Biology:LAPTM4B
 Generic protein structure example |
Lysosomal-associated transmembrane protein 4B is a protein that in humans is encoded by the LAPTM4B gene.[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. 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]
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]
LAPTM4B mediates pro-cancer functions through epidermal growth factor receptor (EGFR), a well-known oncogene overexpressed and/or mutated in many solid tumors. In nutrient rich conditions, LAPTM4B amplifies EGFR signaling by blocking the intraluminal sorting and lysosomal degradation of activated EGFR.[4] In stressed conditions such as nutrient deprivation, LAPTM4B alternatively sequesters inactive EGFR at an endosomal complex that contributes to autophagy upregulation, a function independent of EGFR tyrosine kinase activity.[5] LAPTM4B selectively interacts with inactive EGFR, which is markedly promoted by serum starvation.[5] Thus, LAPTM4B not only augments proliferative signaling, but it also increases cellular stress resistance. These studies suggest that co-targeting EGFR with LAPTM4B or autophagy might improve therapeutic response in EGFR positive cancer patients.
References
- ↑ "Entrez Gene: LAPTM4B lysosomal associated protein transmembrane 4 beta". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55353.
- ↑ 2.0 2.1 "Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer". Nature Medicine 16 (2): 214–218. February 2010. doi:10.1038/nm.2090. PMID 20098429.
- ↑ "Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells". Cancer Research 71 (24): 7481–7489. December 2011. doi:10.1158/0008-5472.CAN-11-0940. PMID 22037872.
- ↑ "LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation". The EMBO Journal 34 (4): 475–490. February 2015. doi:10.15252/embj.201489425. PMID 25588945.
- ↑ 5.0 5.1 "A kinase-independent role for EGF receptor in autophagy initiation" (in English). Cell 160 (1–2): 145–160. January 2015. doi:10.1016/j.cell.2014.12.006. PMID 25594178.
Further reading
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–1795. November 2000. doi:10.1101/gr.143000. PMID 11076863.
- "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research 11 (3): 422–435. March 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia". Genesis 35 (3): 143–152. March 2003. doi:10.1002/gene.10177. PMID 12640618.
- "Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma". Oncogene 22 (32): 5060–5069. August 2003. doi:10.1038/sj.onc.1206832. PMID 12902989.
- "Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma". World Journal of Gastroenterology 10 (11): 1555–1559. June 2004. doi:10.3748/wjg.v10.i11.1555. PMID 15162524.
- "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–2144. October 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression". Cancer Letters 224 (1): 93–103. June 2005. doi:10.1016/j.canlet.2004.10.004. PMID 15911104.
- "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 Research 12 (2): 117–126. 2007. doi:10.1093/dnares/12.2.117. PMID 16303743.
- "The LIFEdb database in 2006". Nucleic Acids Research 34 (Database issue): D415–D418. January 2006. doi:10.1093/nar/gkj139. PMID 16381901.
- "MATN and LAPTM are parts of larger transcription units produced by intergenic splicing: intergenic splicing may be a common phenomenon". DNA Research 12 (5): 365–372. 2007. doi:10.1093/dnares/dsi017. PMID 16769693.
- "Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer". Annals of Oncology 18 (2): 311–316. February 2007. doi:10.1093/annonc/mdl394. PMID 17074969.
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