Lysosomal-associated transmembrane protein 4B is a protein that in humans is encoded by the LAPTM4Bgene.[1]
LAPTM4B protein contains a lysosome localization motif and localizes on late endosomes and lysosomes.
Clinical significance
Increased expression of LAPTM4B has been found in breast, liver, lung, ovarian, uterine, gastric cancers. Elevated LAPTM4B level contributes to chemotherapy resistance in breast cancer. It was found that overexpression of LAPTM4B causes anthracyclines (doxorubicin, daunorubicin, and epirubicin) resistance by retaining drug in the cytoplasm and decreasing nuclear localization of drug and drug induced DNA damage.[2]
In 2011, the same group reported that LAPTM4B also promotes autophagy, a cell survival mechanism mediated by lysosomes. LAPTM4B promotes autophagy and renders tumor cells resistant to metabolic and genotoxic stress and results in more rapid tumor growth.[3]
Based on these findings, LAPTM4B can be utilized to be a therapeutic target to prevent chemotherapy resistance or a marker to identify the patients who will not benefit from anthracyclines.[2]
With S, Rice T, Salinas C, Auld V (2003). "Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia". Genesis. 35 (3): 143–52. doi:10.1002/gene.10177. PMID12640618.
Shao GZ, Zhou RL, Zhang QY, et al. (2003). "Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma". Oncogene. 22 (32): 5060–9. doi:10.1038/sj.onc.1206832. PMID12902989.
Liu XR, Zhou RL, Zhang QY, et al. (2004). "Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma". World J. Gastroenterol. 10 (11): 1555–9. PMID15162524.
Kasper G, Vogel A, Klaman I, et al. (2005). "The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression". Cancer Lett. 224 (1): 93–103. doi:10.1016/j.canlet.2004.10.004. PMID15911104.
Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID16303743.
Maeda K, Horikoshi T, Nakashima E, et al. (2007). "MATN and LAPTM are parts of larger transcription units produced by intergenic splicing: intergenic splicing may be a common phenomenon". DNA Res. 12 (5): 365–72. doi:10.1093/dnares/dsi017. PMID16769693.
Liu Y, Zhang QY, Qian N, Zhou RL (2007). "Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer". Ann. Oncol. 18 (2): 311–6. doi:10.1093/annonc/mdl394. PMID17074969.
