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{{Infobox_gene}}
{{PBB_Controls
'''Protein Wnt-5a''' is a [[protein]] that in humans is encoded by the ''WNT5A'' [[gene]].<ref name="pmid8288227">{{cite journal | vauthors = Clark CC, Cohen I, Eichstetter I, Cannizzaro LA, McPherson JD, Wasmuth JJ, Iozzo RV | title = Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21 | journal = Genomics | volume = 18 | issue = 2 | pages = 249–60 | date = November 1993 | pmid = 8288227 | pmc =  | doi = 10.1006/geno.1993.1463 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: WNT5A wingless-type MMTV integration site family, member 5A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7474| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Wingless-type MMTV integration site family, member 5A
| HGNCid = 12784
| Symbol = WNT5A
| AltSymbols =; hWNT5A
| OMIM = 164975
| ECnumber = 
| Homologene = 20720
| MGIid = 98958
| Function = {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0005102 |text = receptor binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0005625 |text = soluble fraction}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007223 |text = Wnt receptor signaling pathway, calcium modulating pathway}} {{GNF_GO|id=GO:0007254 |text = JNK cascade}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0009653 |text = anatomical structure morphogenesis}} {{GNF_GO|id=GO:0009790 |text = embryonic development}} {{GNF_GO|id=GO:0030324 |text = lung development}} {{GNF_GO|id=GO:0030326 |text = embryonic limb morphogenesis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7474
    | Hs_Ensembl = ENSG00000114251
    | Hs_RefseqProtein = NP_003383
    | Hs_RefseqmRNA = NM_003392
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 55479112
    | Hs_GenLoc_end = 55489996
    | Hs_Uniprot = P41221
    | Mm_EntrezGene = 22418
    | Mm_Ensembl = ENSMUSG00000021994
    | Mm_RefseqmRNA = NM_009524
    | Mm_RefseqProtein = NP_033550
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 14
    | Mm_GenLoc_start = 27332339
    | Mm_GenLoc_end = 27352300
    | Mm_Uniprot = Q8BM17
  }}
}}
'''Wingless-type MMTV integration site family, member 5A''', also known as '''WNT5A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: WNT5A wingless-type MMTV integration site family, member 5A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7474| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The WNT gene family consists of structurally related genes that encode secreted signaling lipid modified [[glycoprotein]]s. These proteins have been implicated in [[oncogenesis]] and in several developmental processes, including regulation of cell fate and patterning during [[embryogenesis]].<ref name="Bhatt2014">{{cite journal | vauthors = Bhatt PM, Malgor R | title = Wnt5a: a player in the pathogenesis of atherosclerosis and other inflammatory disorders | journal = Atherosclerosis | volume = 237 | issue = 1 | pages = 155–62 | date = November 2014 | pmid = 25240110 | doi = 10.1016/j.atherosclerosis.2014.08.027 | pmc=4252768}}</ref> This gene is a member of the WNT gene family. The WNT5A is highly expressed in the [[dermal papilla]] of depilated skin. It encodes a protein showing 98%, 98%, and 87% amino acid identity to the mouse, rat and the xenopus Wnt5a protein, respectively. Wnts, specifically Wnt5a, have also been positively correlated and implicated in inflammatory diseases such as rheumatoid arthritis, tuberculosis, and atherosclerosis.  A central player and active secretor of Wnt5a in both cancer and these inflammatory diseases are macrophages.<ref>{{Cite journal|last=Blumenthal|first=Antje|last2=Ehlers|first2=Stefan|last3=Lauber|first3=Jörg|last4=Buer|first4=Jan|last5=Lange|first5=Christoph|last6=Goldmann|first6=Torsten|last7=Heine|first7=Holger|last8=Brandt|first8=Ernst|last9=Reiling|first9=Norbert|date=2006-08-01|title=The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation|url=http://www.bloodjournal.org/content/108/3/965|journal=Blood|language=en|volume=108|issue=3|pages=965–973|doi=10.1182/blood-2005-12-5046|issn=0006-4971|pmid=16601243}}</ref><ref>{{Cite journal|last=Sen|first=Malini|last2=Chamorro|first2=Mario|last3=Reifert|first3=Jack|last4=Corr|first4=Maripat|last5=Carson|first5=Dennis A.|date=2001-04-01|title=Blockade of Wnt-5A/Frizzled 5 signaling inhibits rheumatoid synoviocyte activation|url=http://onlinelibrary.wiley.com/doi/10.1002/1529-0131(200104)44:43.0.CO;2-L/abstract|journal=Arthritis & Rheumatism|language=en|volume=44|issue=4|pages=772–781|doi=10.1002/1529-0131(200104)44:43.0.CO;2-L|issn=1529-0131}}</ref> Experiments performed in Xenopus laevis embryos have identified that human frizzled-5 (hFz5) is the receptor for the Wnt5a ligand and the Wnt5a/hFz5 signaling mediates axis induction.<ref name="entrez"/> However, non-canonical Wnt5a has also been shown to bind to Ror1/2, RYK, and RTK depending on cell and receptor context to mediate a variety of functions ranging from cell proliferation, polarity, differentiation and apoptosis.<ref>{{Cite journal|last=Gordon|first=Michael D.|last2=Nusse|first2=Roel|date=2006-08-11|title=Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors|url=http://www.jbc.org/content/281/32/22429|journal=Journal of Biological Chemistry|language=en|volume=281|issue=32|pages=22429–22433|doi=10.1074/jbc.R600015200|issn=0021-9258|pmid=16793760}}</ref><ref>{{Cite journal|last=Mikels|first=Amanda|last2=Minami|first2=Yasuhiro|last3=Nusse|first3=Roel|date=2009-10-30|title=Ror2 Receptor Requires Tyrosine Kinase Activity to Mediate Wnt5A Signaling|url=http://www.jbc.org/content/284/44/30167|journal=Journal of Biological Chemistry|language=en|volume=284|issue=44|pages=30167–30176|doi=10.1074/jbc.M109.041715|issn=0021-9258|pmc=2781572|pmid=19720827}}</ref>
{{PBB_Summary
 
| section_title =
=== Development ===
| summary_text = The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 98%, 98% and 87% amino acid identity to the mouse, rat and the xenopus Wnt5A protein, respectively. The experiments performed in Xenopus laevis embryos identified that human frizzled-5 (hFz5) is the receptor for the Wnt5A ligand and the Wnt5A/hFz5 signaling mediates axis induction.<ref name="entrez">{{cite web | title = Entrez Gene: WNT5A wingless-type MMTV integration site family, member 5A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7474| accessdate = }}</ref>
 
}}
The Wnt5a gene is also a key component in posterior development of the female reproductive tract, development of the uterine glands postnatally, and the process of estrogen mediated cellular and molecular responses.<ref name="ReferenceA">{{cite journal | vauthors = Mericskay M, Kitajewski J, Sassoon D | title = Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus | journal = Development | volume = 131 | issue = 9 | pages = 2061–72 | date = May 2004 | pmid = 15073149 | doi = 10.1242/dev.01090 }}</ref> Wnt5a is expressed throughout the endometrial stroma of the mammalian female reproductive tracts and is required in the development of the posterior formation of the Müllerian ducts (cervix, vagina).<ref name="ReferenceB">{{cite journal | vauthors = Hayashi K, Yoshioka S, Reardon SN, Rucker EB, Spencer TE, DeMayo FJ, Lydon JP, MacLean JA | title = WNTs in the neonatal mouse uterus: potential regulation of endometrial gland development | journal = Biology of Reproduction | volume = 84 | issue = 2 | pages = 308–19 | date = February 2011 | pmid = 20962251 | doi = 10.1095/biolreprod.110.088161 | pmc=3071266}}</ref> A Wnt5a absence study was performed by Mericskay et al. on mice and showed the anterior Müllerian-derived structures (oviducts and uterine horns) could easily be identified, and the posterior derived structures (cervix and vagina) were absent showing that this gene is a requirement for its development.<ref name="ReferenceA"/> Other members of the WNT family that are required for the development of the reproductive tract are Wnt4 and Wnt7a.<ref name="ReferenceB"/> Failure to develop reproductive tract will result in infertility. Not only is the WNT5A gene responsible for this formation but also is significate in the postnatal production of the uterine glands otherwise known as adenogenesis which is essential for adult function.<ref name="ReferenceA"/>  In addition to these two developments Wnt5a it needed for the complete process of estrogen mediated cellular and molecular responses.<ref name="ReferenceA"/>
 
== Wnt ligands ==
 
Wnt ligands are classically described as acting in an autocrine/paracrine manner.<ref>{{cite journal | vauthors = Corbett L, Mann J, Mann DA | title = Non-Canonical Wnt Predominates in Activated Rat Hepatic Stellate Cells, Influencing HSC Survival and Paracrine Stimulation of Kupffer Cells | journal = PLoS One | volume = 10 | issue = 11 | pages = e0142794 | date = 2015-01-01 | pmid = 26566235 | pmc = 4643911 | doi = 10.1371/journal.pone.0142794 }}</ref><ref>{{cite journal | vauthors = Clevers H, Nusse R | title = Wnt/β-catenin signaling and disease | journal = Cell | volume = 149 | issue = 6 | pages = 1192–205 | date = June 2012 | pmid = 22682243 | doi = 10.1016/j.cell.2012.05.012 | url = http://linkinghub.elsevier.com/retrieve/pii/S0092867412005867 }}</ref><ref>{{cite journal | vauthors = Anagnostou SH, Shepherd PR | title = Glucose induces an autocrine activation of the Wnt/beta-catenin pathway in macrophage cell lines | language = en | journal = The Biochemical Journal | volume = 416 | issue = 2 | pages = 211–8 | date = December 2008 | pmid = 18823284 | doi = 10.1042/BJ20081426 | url = http://www.biochemj.org/content/416/2/211 }}</ref> Wnts are also hydrophobic with significant post-translational palmitoylation and glycosylation.<ref>{{cite journal | vauthors = Logan CY, Nusse R | title = The Wnt signaling pathway in development and disease | journal = Annual Review of Cell and Developmental Biology | volume = 20 | issue = 1 | pages = 781–810 | date = 2004-10-08 | pmid = 15473860 | doi = 10.1146/annurev.cellbio.20.010403.113126 | url = http://www.annualreviews.org/doi/10.1146/annurev.cellbio.20.010403.113126 }}</ref><ref>{{cite journal | vauthors = Kurayoshi M, Yamamoto H, Izumi S, Kikuchi A | title = Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling | language = en | journal = The Biochemical Journal | volume = 402 | issue = 3 | pages = 515–23 | date = March 2007 | pmid = 17117926 | pmc = 1863570 | doi = 10.1042/BJ20061476 | url = http://www.biochemj.org/content/402/3/515 }}</ref> These post-translational modifications are important for docking to extracellular lipoprotein particles allowing them to travel systemically.<ref>{{cite journal | vauthors = Panáková D, Sprong H, Marois E, Thiele C, Eaton S | title = Lipoprotein particles are required for Hedgehog and Wingless signalling | journal = Nature | volume = 435 | issue = 7038 | pages = 58–65 | date = May 2005 | pmid = 15875013 | doi = 10.1038/nature03504 | url = http://www.nature.com/doifinder/10.1038/nature03504 }}</ref><ref>{{cite journal | vauthors = Neumann S, Coudreuse DY, van der Westhuyzen DR, Eckhardt ER, Korswagen HC, Schmitz G, Sprong H | title = Mammalian Wnt3a is released on lipoprotein particles | language = en | journal = Traffic | volume = 10 | issue = 3 | pages = 334–43 | date = March 2009 | pmid = 19207483 | doi = 10.1111/j.1600-0854.2008.00872.x | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0854.2008.00872.x/abstract }}</ref> Additionally, due to the high degree of sequence homology between Wnts many are characterized by their downstream actions.
 
== Clinical significance ==
 
=== Cancer ===
 
Wnt5a is implicated in many different types of cancers.<ref>{{cite journal | vauthors = Asem MS, Buechler S, Wates RB, Miller DL, Stack MS | title = Wnt5a Signaling in Cancer | language = en | journal = Cancers | volume = 8 | issue = 9 | pages = 79 | date = August 2016 | pmid = 27571105 | pmc = 5040981 | doi = 10.3390/cancers8090079 | url = http://www.mdpi.com/2072-6694/8/9/79 }}</ref> However, no consistent correlation occurs between cancer aggressiveness and Wnt5a signaling up-regulation or down-regulation. Interestingly, the WNT5A gene has been shown to encode two distinct isoforms, each with unique functions in the context of cancer.<ref name=":0">{{cite journal | vauthors = Bauer M, Bénard J, Gaasterland T, Willert K, Cappellen D | title = WNT5A encodes two isoforms with distinct functions in cancers | journal = PLoS One | volume = 8 | issue = 11 | pages = e80526 | pmid = 24260410 | pmc = 3832467 | doi = 10.1371/journal.pone.0080526 | url = http://dx.plos.org/10.1371/journal.pone.0080526 }}</ref> The two isoforms are termed Wnt5a-long (Wnt5a-L) and Wnt5a-short (Wnt5a-S) because Wnt5a-L is 18 amino acids longer than Wnt5a-S.<ref name=":0" /> These 18 amino acids appear to have contrasting roles in cancer. Specifically, Wnt5a-L inhibits proliferation and Wnt5a-S increases proliferation.<ref name=":0" /> This may account for the discrepancies as to the role of Wnt5a in various cancers; however, the significance of these two isoforms is not completely clear.<ref>{{cite journal | vauthors = Kumawat K, Gosens R | title = WNT-5A: signaling and functions in health and disease | language = en | journal = Cellular and Molecular Life Sciences | volume = 73 | issue = 3 | pages = 567–87 | date = February 2016 | pmid = 26514730 | pmc = 4713724 | doi = 10.1007/s00018-015-2076-y | url = https://link.springer.com/article/10.1007/s00018-015-2076-y }}</ref> Elevated levels of beta-catenin in both primary and metastases of malignant melanoma have been correlated to improved survival and a decrease in cell markers of proliferation.<ref>{{Cite journal|last=Chien|first=Andy J.|last2=Moore|first2=Erin C.|last3=Lonsdorf|first3=Anke S.|last4=Kulikauskas|first4=Rima M.|last5=Rothberg|first5=Bonnie Gould|last6=Berger|first6=Aaron J.|last7=Major|first7=Michael B.|last8=Hwang|first8=Sam T.|last9=Rimm|first9=David L.|date=2009-01-27|title=Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model|url=http://www.pnas.org/content/106/4/1193|journal=Proceedings of the National Academy of Sciences|language=en|volume=106|issue=4|pages=1193–1198|doi=10.1073/pnas.0811902106|issn=0027-8424|pmc=2626610|pmid=19144919}}</ref>
 
=== Cardiovascular Disease ===
Increasing evidence has implicated Wnt5a in chronic inflammatory disorders.<ref>{{Cite web|url=https://www.spandidos-publications.com/ijmm/19/2/273/download|title=|last=|first=|date=|website=|publisher=|access-date=}}</ref> In particular Wnt5a has been implicated in atherosclerosis.<ref>{{Cite journal|last=Bhatt|first=Pooja M.|last2=Malgor|first2=Ramiro|title=Wnt5a: A player in the pathogenesis of atherosclerosis and other inflammatory disorders|url=http://linkinghub.elsevier.com/retrieve/pii/S0021915014013549|journal=Atherosclerosis|volume=237|issue=1|pages=155–162|doi=10.1016/j.atherosclerosis.2014.08.027|pmc=4252768|pmid=25240110}}</ref> It has been previously reported that there is an association between Wnt5a mRNA and protein expression and histopathological severity of human atherosclerotic lesions as well as co-expression of Wnt5a and TLR4 in foam cells/macrophages of murine and human atherosclerotic lesions.<ref>{{Cite journal|last=Bhatt|first=Pooja M.|last2=Lewis|first2=Christopher J.|last3=House|first3=Denise L.|last4=Keller|first4=Chad M.|last5=Kohn|first5=Leonard D.|last6=Silver|first6=Mitchell J.|last7=McCall|first7=Kelly D.|last8=Goetz|first8=Douglas J.|last9=Malgor|first9=Ramiro|date=2012-01-01|title=Increased Wnt5a mRNA Expression in Advanced Atherosclerotic Lesions, and Oxidized LDL Treated Human Monocyte-Derived Macrophages|journal=The open circulation & vascular journal|volume=5|pages=1–7|issn=1877-3826|pmc=4270053|pmid=25530821|doi=10.2174/1877382601205010001}}</ref><ref>{{Cite journal|last=Christman|first=Mark A.|last2=Goetz|first2=Douglas J.|last3=Dickerson|first3=Eric|last4=McCall|first4=Kelly D.|last5=Lewis|first5=Christopher J.|last6=Benencia|first6=Fabian|last7=Silver|first7=Mitchell J.|last8=Kohn|first8=Leonard D.|last9=Malgor|first9=Ramiro|date=2008-06-01|title=Wnt5a is expressed in murine and human atherosclerotic lesions|url=http://ajpheart.physiology.org/content/294/6/H2864|journal=American Journal of Physiology.  Heart and Circulatory Physiology|language=en|volume=294|issue=6|pages=H2864–H2870|doi=10.1152/ajpheart.00982.2007|issn=0363-6135|pmid=18456733}}</ref> However, the role of Wnt proteins in the process and development of inflammation in atherosclerosis and other inflammatory conditions is not yet clear.
 
=== Therapeutics ===
Some of the benefits of targeting this signaling pathway include:<ref>{{Cite journal|last=Dihlmann|first=Susanne|last2=von Knebel Doeberitz|first2=Magnus|date=2005-02-10|title=Wnt/β-catenin-pathway as a molecular target for future anti-cancer therapeutics|url=http://onlinelibrary.wiley.com/doi/10.1002/ijc.20609/abstract|journal=International Journal of Cancer|language=en|volume=113|issue=4|pages=515–524|doi=10.1002/ijc.20609|issn=1097-0215}}</ref>
 
• Many of the current DNA-targeting anticancer drugs carry the risk of giving rise to secondary tumors or additional primary cancers.
 
• Preferentially killing rapidly replicating malignant cells via cytotoxic agents cause serious side effects by injuring normal cells, particularly hematopoeitic cells, intestinal cells, hair follicle and germ cells.
 
• Differentiated tumor cells in a state of quiescence are typically not affected by drugs can may account for tumor recurrence.
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Mericskay M, Kitajewski J, Sassoon D | title = Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus | journal = Development | volume = 131 | issue = 9 | pages = 2061–72 | date = May 2004 | pmid = 15073149 | doi = 10.1242/dev.01090 }}
* {{cite journal | vauthors = Hayashi K, Yoshioka S, Reardon SN, Rucker EB, Spencer TE, DeMayo FJ, Lydon JP, MacLean JA | title = WNTs in the neonatal mouse uterus: potential regulation of endometrial gland development | journal = Biology of Reproduction | volume = 84 | issue = 2 | pages = 308–19 | date = February 2011 | pmid = 20962251 | doi = 10.1095/biolreprod.110.088161 | pmc=3071266}}
* {{cite journal | title = Wnt5a | journal = Signaling Gateway Molecule Pages | url = http://www.signaling-gateway.org/molecule/query?afcsid=A002385 }}
* {{cite journal | vauthors = Smolich BD, McMahon JA, McMahon AP, Papkoff J | title = Wnt family proteins are secreted and associated with the cell surface | journal = Molecular Biology of the Cell | volume = 4 | issue = 12 | pages = 1267–75 | date = December 1993 | pmid = 8167409 | pmc = 275763 | doi = 10.1091/mbc.4.12.1267 }}
* {{cite journal | vauthors = Danielson KG, Pillarisetti J, Cohen IR, Sholehvar B, Huebner K, Ng LJ, Nicholls JM, Cheah KS, Iozzo RV | title = Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis | journal = The Journal of Biological Chemistry | volume = 270 | issue = 52 | pages = 31225–34 | date = December 1995 | pmid = 8537388 | doi = 10.1074/jbc.270.52.31225 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus H | title = A member of the Frizzled protein family mediating axis induction by Wnt-5A | journal = Science | volume = 275 | issue = 5306 | pages = 1652–4 | date = March 1997 | pmid = 9054360 | doi = 10.1126/science.275.5306.1652 }}
* {{cite journal | vauthors = Wright M, Aikawa M, Szeto W, Papkoff J | title = Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells | journal = Biochemical and Biophysical Research Communications | volume = 263 | issue = 2 | pages = 384–8 | date = September 1999 | pmid = 10491302 | doi = 10.1006/bbrc.1999.1344 }}
* {{cite journal | vauthors = Gazit A, Yaniv A, Bafico A, Pramila T, Igarashi M, Kitajewski J, Aaronson SA | title = Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response | journal = Oncogene | volume = 18 | issue = 44 | pages = 5959–66 | date = October 1999 | pmid = 10557084 | doi = 10.1038/sj.onc.1202985 }}
* {{cite journal | vauthors = Saitoh T, Mine T, Katoh M | title = Frequent up-regulation of WNT5A mRNA in primary gastric cancer | journal = International Journal of Molecular Medicine | volume = 9 | issue = 5 | pages = 515–9 | date = May 2002 | pmid = 11956659 | doi = 10.3892/ijmm.9.5.515 }}
* {{cite journal | vauthors = Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M, Trent JM | title = Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma | journal = Cancer Cell | volume = 1 | issue = 3 | pages = 279–88 | date = April 2002 | pmid = 12086864 | doi = 10.1016/S1535-6108(02)00045-4 }}
* {{cite journal | vauthors = Saitoh T, Katoh M | title = Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells | journal = International Journal of Molecular Medicine | volume = 10 | issue = 3 | pages = 345–9 | date = September 2002 | pmid = 12165812 | doi = 10.3892/ijmm.10.3.345 }}
* {{cite journal | vauthors = Murphy LL, Hughes CC | title = Endothelial cells stimulate T cell NFAT nuclear translocation in the presence of cyclosporin A: involvement of the wnt/glycogen synthase kinase-3 beta pathway | journal = Journal of Immunology | volume = 169 | issue = 7 | pages = 3717–25 | date = October 2002 | pmid = 12244165 | doi = 10.4049/jimmunol.169.7.3717 }}
* {{cite journal | vauthors = Thrasivoulou C, Millar M, Ahmed A | title = Activation of intracellular calcium by multiple Wnt ligands and translocation of β-catenin into the nucleus: a convergent model of Wnt/Ca2+ and Wnt/β-catenin pathways | journal = The Journal of Biological Chemistry | volume = 288 | issue = 50 | pages = 35651–9 | date = December 2013 | pmid = 24158438 | doi = 10.1074/jbc.M112.437913 | pmc=3861617}}
* {{cite journal | vauthors = Ishitani T, Kishida S, Hyodo-Miura J, Ueno N, Yasuda J, Waterman M, Shibuya H, Moon RT, Ninomiya-Tsuji J, Matsumoto K | title = The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling | journal = Molecular and Cellular Biology | volume = 23 | issue = 1 | pages = 131–9 | date = January 2003 | pmid = 12482967 | pmc = 140665 | doi = 10.1128/MCB.23.1.131-139.2003 }}
* {{cite journal | vauthors = Hocevar BA, Mou F, Rennolds JL, Morris SM, Cooper JA, Howe PH | title = Regulation of the Wnt signaling pathway by disabled-2 (Dab2) | journal = The EMBO Journal | volume = 22 | issue = 12 | pages = 3084–94 | date = June 2003 | pmid = 12805222 | pmc = 162138 | doi = 10.1093/emboj/cdg286 }}
* {{cite journal | vauthors = Taki M, Kamata N, Yokoyama K, Fujimoto R, Tsutsumi S, Nagayama M | title = Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells | journal = Cancer Science | volume = 94 | issue = 7 | pages = 593–7 | date = July 2003 | pmid = 12841867 | doi = 10.1111/j.1349-7006.2003.tb01488.x }}
* {{cite journal | vauthors = Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL | title = Gene expression profiling predicts clinical outcome of prostate cancer | journal = The Journal of Clinical Investigation | volume = 113 | issue = 6 | pages = 913–23 | date = March 2004 | pmid = 15067324 | pmc = 362118 | doi = 10.1172/JCI20032 }}
* {{cite journal | vauthors = Nishioka K, Dennis JE, Gao J, Goldberg VM, Caplan AI | title = Sustained Wnt protein expression in chondral constructs from mesenchymal stem cells | journal = Journal of Cellular Physiology | volume = 203 | issue = 1 | pages = 6–14 | date = April 2005 | pmid = 15389636 | doi = 10.1002/jcp.20196 }}
* {{cite journal | vauthors = Blanc E, Roux GL, Bénard J, Raguénez G | title = Low expression of Wnt-5a gene is associated with high-risk neuroblastoma | journal = Oncogene | volume = 24 | issue = 7 | pages = 1277–83 | date = February 2005 | pmid = 15592517 | doi = 10.1038/sj.onc.1208255 }}
* {{cite journal | vauthors = Kremenevskaja N, von Wasielewski R, Rao AS, Schöfl C, Andersson T, Brabant G | title = Wnt-5a has tumor suppressor activity in thyroid carcinoma | journal = Oncogene | volume = 24 | issue = 13 | pages = 2144–54 | date = March 2005 | pmid = 15735754 | doi = 10.1038/sj.onc.1208370 }}
* {{cite journal | vauthors = Wang Q, Symes AJ, Kane CA, Freeman A, Nariculam J, Munson P, Thrasivoulou C, Masters JR, Ahmed A | title = A novel role for Wnt/Ca2+ signaling in actin cytoskeleton remodeling and cell motility in prostate cancer | journal = PLoS One | volume = 5 | issue = 5 | pages = e10456 | date = May 2010 | pmid = 20454608 | pmc = 2864254 | doi = 10.1371/journal.pone.0010456 | editor1-last = Hotchin | bibcode = 2010PLoSO...510456W | editor1-first = Neil A. }}


==References==
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Smolich BD, McMahon JA, McMahon AP, Papkoff J |title=Wnt family proteins are secreted and associated with the cell surface. |journal=Mol. Biol. Cell |volume=4 |issue= 12 |pages= 1267-75 |year= 1994 |pmid= 8167409 |doi=  }}
*{{cite journal  | author=Clark CC, Cohen I, Eichstetter I, ''et al.'' |title=Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21. |journal=Genomics |volume=18 |issue= 2 |pages= 249-60 |year= 1994 |pmid= 8288227 |doi= 10.1006/geno.1993.1463 }}
*{{cite journal  | author=Danielson KG, Pillarisetti J, Cohen IR, ''et al.'' |title=Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis. |journal=J. Biol. Chem. |volume=270 |issue= 52 |pages= 31225-34 |year= 1996 |pmid= 8537388 |doi=  }}
*{{cite journal  | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi=  }}
*{{cite journal  | author=He X, Saint-Jeannet JP, Wang Y, ''et al.'' |title=A member of the Frizzled protein family mediating axis induction by Wnt-5A. |journal=Science |volume=275 |issue= 5306 |pages= 1652-4 |year= 1997 |pmid= 9054360 |doi=  }}
*{{cite journal  | author=Wright M, Aikawa M, Szeto W, Papkoff J |title=Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells. |journal=Biochem. Biophys. Res. Commun. |volume=263 |issue= 2 |pages= 384-8 |year= 1999 |pmid= 10491302 |doi= 10.1006/bbrc.1999.1344 }}
*{{cite journal  | author=Gazit A, Yaniv A, Bafico A, ''et al.'' |title=Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response. |journal=Oncogene |volume=18 |issue= 44 |pages= 5959-66 |year= 1999 |pmid= 10557084 |doi= 10.1038/sj.onc.1202985 }}
*{{cite journal  | author=Saitoh T, Mine T, Katoh M |title=Frequent up-regulation of WNT5A mRNA in primary gastric cancer. |journal=Int. J. Mol. Med. |volume=9 |issue= 5 |pages= 515-9 |year= 2002 |pmid= 11956659 |doi=  }}
*{{cite journal  | author=Weeraratna AT, Jiang Y, Hostetter G, ''et al.'' |title=Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. |journal=Cancer Cell |volume=1 |issue= 3 |pages= 279-88 |year= 2002 |pmid= 12086864 |doi=  }}
*{{cite journal  | author=Saitoh T, Katoh M |title=Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells. |journal=Int. J. Mol. Med. |volume=10 |issue= 3 |pages= 345-9 |year= 2003 |pmid= 12165812 |doi=  }}
*{{cite journal  | author=Murphy LL, Hughes CC |title=Endothelial cells stimulate T cell NFAT nuclear translocation in the presence of cyclosporin A: involvement of the wnt/glycogen synthase kinase-3 beta pathway. |journal=J. Immunol. |volume=169 |issue= 7 |pages= 3717-25 |year= 2002 |pmid= 12244165 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Ishitani T, Kishida S, Hyodo-Miura J, ''et al.'' |title=The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling. |journal=Mol. Cell. Biol. |volume=23 |issue= 1 |pages= 131-9 |year= 2003 |pmid= 12482967 |doi=  }}
*{{cite journal  | author=Hocevar BA, Mou F, Rennolds JL, ''et al.'' |title=Regulation of the Wnt signaling pathway by disabled-2 (Dab2). |journal=EMBO J. |volume=22 |issue= 12 |pages= 3084-94 |year= 2003 |pmid= 12805222 |doi= 10.1093/emboj/cdg286 }}
*{{cite journal  | author=Taki M, Kamata N, Yokoyama K, ''et al.'' |title=Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells. |journal=Cancer Sci. |volume=94 |issue= 7 |pages= 593-7 |year= 2004 |pmid= 12841867 |doi=  }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Glinsky GV, Glinskii AB, Stephenson AJ, ''et al.'' |title=Gene expression profiling predicts clinical outcome of prostate cancer. |journal=J. Clin. Invest. |volume=113 |issue= 6 |pages= 913-23 |year= 2004 |pmid= 15067324 |doi= 10.1172/JCI200420032 }}
*{{cite journal  | author=Nishioka K, Dennis JE, Gao J, ''et al.'' |title=Sustained Wnt protein expression in chondral constructs from mesenchymal stem cells. |journal=J. Cell. Physiol. |volume=203 |issue= 1 |pages= 6-14 |year= 2005 |pmid= 15389636 |doi= 10.1002/jcp.20196 }}
*{{cite journal  | author=Blanc E, Roux GL, Bénard J, Raguénez G |title=Low expression of Wnt-5a gene is associated with high-risk neuroblastoma. |journal=Oncogene |volume=24 |issue= 7 |pages= 1277-83 |year= 2005 |pmid= 15592517 |doi= 10.1038/sj.onc.1208255 }}
*{{cite journal  | author=Kremenevskaja N, von Wasielewski R, Rao AS, ''et al.'' |title=Wnt-5a has tumor suppressor activity in thyroid carcinoma. |journal=Oncogene |volume=24 |issue= 13 |pages= 2144-54 |year= 2005 |pmid= 15735754 |doi= 10.1038/sj.onc.1208370 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{Wnt signaling pathway}}
{{WikiDoc Sources}}

Revision as of 02:08, 25 October 2017

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Protein Wnt-5a is a protein that in humans is encoded by the WNT5A gene.[1][2]

Function

The WNT gene family consists of structurally related genes that encode secreted signaling lipid modified glycoproteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis.[3] This gene is a member of the WNT gene family. The WNT5A is highly expressed in the dermal papilla of depilated skin. It encodes a protein showing 98%, 98%, and 87% amino acid identity to the mouse, rat and the xenopus Wnt5a protein, respectively. Wnts, specifically Wnt5a, have also been positively correlated and implicated in inflammatory diseases such as rheumatoid arthritis, tuberculosis, and atherosclerosis. A central player and active secretor of Wnt5a in both cancer and these inflammatory diseases are macrophages.[4][5] Experiments performed in Xenopus laevis embryos have identified that human frizzled-5 (hFz5) is the receptor for the Wnt5a ligand and the Wnt5a/hFz5 signaling mediates axis induction.[2] However, non-canonical Wnt5a has also been shown to bind to Ror1/2, RYK, and RTK depending on cell and receptor context to mediate a variety of functions ranging from cell proliferation, polarity, differentiation and apoptosis.[6][7]

Development

The Wnt5a gene is also a key component in posterior development of the female reproductive tract, development of the uterine glands postnatally, and the process of estrogen mediated cellular and molecular responses.[8] Wnt5a is expressed throughout the endometrial stroma of the mammalian female reproductive tracts and is required in the development of the posterior formation of the Müllerian ducts (cervix, vagina).[9] A Wnt5a absence study was performed by Mericskay et al. on mice and showed the anterior Müllerian-derived structures (oviducts and uterine horns) could easily be identified, and the posterior derived structures (cervix and vagina) were absent showing that this gene is a requirement for its development.[8] Other members of the WNT family that are required for the development of the reproductive tract are Wnt4 and Wnt7a.[9] Failure to develop reproductive tract will result in infertility. Not only is the WNT5A gene responsible for this formation but also is significate in the postnatal production of the uterine glands otherwise known as adenogenesis which is essential for adult function.[8] In addition to these two developments Wnt5a it needed for the complete process of estrogen mediated cellular and molecular responses.[8]

Wnt ligands

Wnt ligands are classically described as acting in an autocrine/paracrine manner.[10][11][12] Wnts are also hydrophobic with significant post-translational palmitoylation and glycosylation.[13][14] These post-translational modifications are important for docking to extracellular lipoprotein particles allowing them to travel systemically.[15][16] Additionally, due to the high degree of sequence homology between Wnts many are characterized by their downstream actions.

Clinical significance

Cancer

Wnt5a is implicated in many different types of cancers.[17] However, no consistent correlation occurs between cancer aggressiveness and Wnt5a signaling up-regulation or down-regulation. Interestingly, the WNT5A gene has been shown to encode two distinct isoforms, each with unique functions in the context of cancer.[18] The two isoforms are termed Wnt5a-long (Wnt5a-L) and Wnt5a-short (Wnt5a-S) because Wnt5a-L is 18 amino acids longer than Wnt5a-S.[18] These 18 amino acids appear to have contrasting roles in cancer. Specifically, Wnt5a-L inhibits proliferation and Wnt5a-S increases proliferation.[18] This may account for the discrepancies as to the role of Wnt5a in various cancers; however, the significance of these two isoforms is not completely clear.[19] Elevated levels of beta-catenin in both primary and metastases of malignant melanoma have been correlated to improved survival and a decrease in cell markers of proliferation.[20]

Cardiovascular Disease

Increasing evidence has implicated Wnt5a in chronic inflammatory disorders.[21] In particular Wnt5a has been implicated in atherosclerosis.[22] It has been previously reported that there is an association between Wnt5a mRNA and protein expression and histopathological severity of human atherosclerotic lesions as well as co-expression of Wnt5a and TLR4 in foam cells/macrophages of murine and human atherosclerotic lesions.[23][24] However, the role of Wnt proteins in the process and development of inflammation in atherosclerosis and other inflammatory conditions is not yet clear.

Therapeutics

Some of the benefits of targeting this signaling pathway include:[25]

• Many of the current DNA-targeting anticancer drugs carry the risk of giving rise to secondary tumors or additional primary cancers.

• Preferentially killing rapidly replicating malignant cells via cytotoxic agents cause serious side effects by injuring normal cells, particularly hematopoeitic cells, intestinal cells, hair follicle and germ cells.

• Differentiated tumor cells in a state of quiescence are typically not affected by drugs can may account for tumor recurrence.

References

  1. ↑ Clark CC, Cohen I, Eichstetter I, Cannizzaro LA, McPherson JD, Wasmuth JJ, Iozzo RV (November 1993). "Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21". Genomics. 18 (2): 249–60. doi:10.1006/geno.1993.1463. PMID 8288227.
  2. ↑ 2.0 2.1 "Entrez Gene: WNT5A wingless-type MMTV integration site family, member 5A".
  3. ↑ Bhatt PM, Malgor R (November 2014). "Wnt5a: a player in the pathogenesis of atherosclerosis and other inflammatory disorders". Atherosclerosis. 237 (1): 155–62. doi:10.1016/j.atherosclerosis.2014.08.027. PMC 4252768. PMID 25240110.
  4. ↑ Blumenthal, Antje; Ehlers, Stefan; Lauber, Jörg; Buer, Jan; Lange, Christoph; Goldmann, Torsten; Heine, Holger; Brandt, Ernst; Reiling, Norbert (2006-08-01). "The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation". Blood. 108 (3): 965–973. doi:10.1182/blood-2005-12-5046. ISSN 0006-4971. PMID 16601243.
  5. ↑ Sen, Malini; Chamorro, Mario; Reifert, Jack; Corr, Maripat; Carson, Dennis A. (2001-04-01). "Blockade of Wnt-5A/Frizzled 5 signaling inhibits rheumatoid synoviocyte activation". Arthritis & Rheumatism. 44 (4): 772–781. doi:10.1002/1529-0131(200104)44:43.0.CO;2-L. ISSN 1529-0131.
  6. ↑ Gordon, Michael D.; Nusse, Roel (2006-08-11). "Wnt Signaling: Multiple Pathways, Multiple Receptors, and Multiple Transcription Factors". Journal of Biological Chemistry. 281 (32): 22429–22433. doi:10.1074/jbc.R600015200. ISSN 0021-9258. PMID 16793760.
  7. ↑ Mikels, Amanda; Minami, Yasuhiro; Nusse, Roel (2009-10-30). "Ror2 Receptor Requires Tyrosine Kinase Activity to Mediate Wnt5A Signaling". Journal of Biological Chemistry. 284 (44): 30167–30176. doi:10.1074/jbc.M109.041715. ISSN 0021-9258. PMC 2781572. PMID 19720827.
  8. ↑ 8.0 8.1 8.2 8.3 Mericskay M, Kitajewski J, Sassoon D (May 2004). "Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus". Development. 131 (9): 2061–72. doi:10.1242/dev.01090. PMID 15073149.
  9. ↑ 9.0 9.1 Hayashi K, Yoshioka S, Reardon SN, Rucker EB, Spencer TE, DeMayo FJ, Lydon JP, MacLean JA (February 2011). "WNTs in the neonatal mouse uterus: potential regulation of endometrial gland development". Biology of Reproduction. 84 (2): 308–19. doi:10.1095/biolreprod.110.088161. PMC 3071266. PMID 20962251.
  10. ↑ Corbett L, Mann J, Mann DA (2015-01-01). "Non-Canonical Wnt Predominates in Activated Rat Hepatic Stellate Cells, Influencing HSC Survival and Paracrine Stimulation of Kupffer Cells". PLoS One. 10 (11): e0142794. doi:10.1371/journal.pone.0142794. PMC 4643911. PMID 26566235.
  11. ↑ Clevers H, Nusse R (June 2012). "Wnt/β-catenin signaling and disease". Cell. 149 (6): 1192–205. doi:10.1016/j.cell.2012.05.012. PMID 22682243.
  12. ↑ Anagnostou SH, Shepherd PR (December 2008). "Glucose induces an autocrine activation of the Wnt/beta-catenin pathway in macrophage cell lines". The Biochemical Journal. 416 (2): 211–8. doi:10.1042/BJ20081426. PMID 18823284.
  13. ↑ Logan CY, Nusse R (2004-10-08). "The Wnt signaling pathway in development and disease". Annual Review of Cell and Developmental Biology. 20 (1): 781–810. doi:10.1146/annurev.cellbio.20.010403.113126. PMID 15473860.
  14. ↑ Kurayoshi M, Yamamoto H, Izumi S, Kikuchi A (March 2007). "Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling". The Biochemical Journal. 402 (3): 515–23. doi:10.1042/BJ20061476. PMC 1863570. PMID 17117926.
  15. ↑ Panáková D, Sprong H, Marois E, Thiele C, Eaton S (May 2005). "Lipoprotein particles are required for Hedgehog and Wingless signalling". Nature. 435 (7038): 58–65. doi:10.1038/nature03504. PMID 15875013.
  16. ↑ Neumann S, Coudreuse DY, van der Westhuyzen DR, Eckhardt ER, Korswagen HC, Schmitz G, Sprong H (March 2009). "Mammalian Wnt3a is released on lipoprotein particles". Traffic. 10 (3): 334–43. doi:10.1111/j.1600-0854.2008.00872.x. PMID 19207483.
  17. ↑ Asem MS, Buechler S, Wates RB, Miller DL, Stack MS (August 2016). "Wnt5a Signaling in Cancer". Cancers. 8 (9): 79. doi:10.3390/cancers8090079. PMC 5040981. PMID 27571105.
  18. ↑ 18.0 18.1 18.2 Bauer M, Bénard J, Gaasterland T, Willert K, Cappellen D. "WNT5A encodes two isoforms with distinct functions in cancers". PLoS One. 8 (11): e80526. doi:10.1371/journal.pone.0080526. PMC 3832467. PMID 24260410.
  19. ↑ Kumawat K, Gosens R (February 2016). "WNT-5A: signaling and functions in health and disease". Cellular and Molecular Life Sciences. 73 (3): 567–87. doi:10.1007/s00018-015-2076-y. PMC 4713724. PMID 26514730.
  20. ↑ Chien, Andy J.; Moore, Erin C.; Lonsdorf, Anke S.; Kulikauskas, Rima M.; Rothberg, Bonnie Gould; Berger, Aaron J.; Major, Michael B.; Hwang, Sam T.; Rimm, David L. (2009-01-27). "Activated Wnt/ß-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model". Proceedings of the National Academy of Sciences. 106 (4): 1193–1198. doi:10.1073/pnas.0811902106. ISSN 0027-8424. PMC 2626610. PMID 19144919.
  21. ↑ https://www.spandidos-publications.com/ijmm/19/2/273/download. Missing or empty |title= (help)
  22. ↑ Bhatt, Pooja M.; Malgor, Ramiro. "Wnt5a: A player in the pathogenesis of atherosclerosis and other inflammatory disorders". Atherosclerosis. 237 (1): 155–162. doi:10.1016/j.atherosclerosis.2014.08.027. PMC 4252768. PMID 25240110.
  23. ↑ Bhatt, Pooja M.; Lewis, Christopher J.; House, Denise L.; Keller, Chad M.; Kohn, Leonard D.; Silver, Mitchell J.; McCall, Kelly D.; Goetz, Douglas J.; Malgor, Ramiro (2012-01-01). "Increased Wnt5a mRNA Expression in Advanced Atherosclerotic Lesions, and Oxidized LDL Treated Human Monocyte-Derived Macrophages". The open circulation & vascular journal. 5: 1–7. doi:10.2174/1877382601205010001. ISSN 1877-3826. PMC 4270053. PMID 25530821.
  24. ↑ Christman, Mark A.; Goetz, Douglas J.; Dickerson, Eric; McCall, Kelly D.; Lewis, Christopher J.; Benencia, Fabian; Silver, Mitchell J.; Kohn, Leonard D.; Malgor, Ramiro (2008-06-01). "Wnt5a is expressed in murine and human atherosclerotic lesions". American Journal of Physiology. Heart and Circulatory Physiology. 294 (6): H2864–H2870. doi:10.1152/ajpheart.00982.2007. ISSN 0363-6135. PMID 18456733.
  25. ↑ Dihlmann, Susanne; von Knebel Doeberitz, Magnus (2005-02-10). "Wnt/β-catenin-pathway as a molecular target for future anti-cancer therapeutics". International Journal of Cancer. 113 (4): 515–524. doi:10.1002/ijc.20609. ISSN 1097-0215.

Further reading

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