LAPTM4B

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.{{cite journal | vauthors = Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, Desmedt C, Sotiriou C, Szallasi Z, Iglehart JD, Richardson AL, Wang ZC | display-authors = 6 | title = Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer | journal = Nature Medicine | volume = 16 | issue = 2 | pages = 214–218 | date = February 2010 | pmid = 20098429 | pmc = 2826790 | doi = 10.1038/nm.2090 }}

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.{{cite journal | vauthors = Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, Wang ZC, Richardson AL | display-authors = 6 | title = Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells | journal = Cancer Research | volume = 71 | issue = 24 | pages = 7481–7489 | date = December 2011 | pmid = 22037872 | pmc = 3261660 | doi = 10.1158/0008-5472.CAN-11-0940 }} 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.

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.{{cite journal | vauthors = Tan X, Sun Y, Thapa N, Liao Y, Hedman AC, Anderson RA | title = LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation | journal = The EMBO Journal | volume = 34 | issue = 4 | pages = 475–490 | date = February 2015 | pmid = 25588945 | pmc = 4331002 | doi = 10.15252/embj.201489425 }} 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.{{cite journal | vauthors = Tan X, Thapa N, Sun Y, Anderson RA | title = A kinase-independent role for EGF receptor in autophagy initiation | language = English | journal = Cell | volume = 160 | issue = 1–2 | pages = 145–160 | date = January 2015 | pmid = 25594178 | pmc = 4297316 | doi = 10.1016/j.cell.2014.12.006 }} LAPTM4B selectively interacts with inactive EGFR, which is markedly promoted by serum starvation. 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.

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• {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–1795 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
• {{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | display-authors = 6 | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–435 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}
• {{cite journal | vauthors = With S, Rice T, Salinas C, Auld V | title = Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia | journal = Genesis | volume = 35 | issue = 3 | pages = 143–152 | date = March 2003 | pmid = 12640618 | doi = 10.1002/gene.10177 | s2cid = 29252213 }}
• {{cite journal | vauthors = Shao GZ, Zhou RL, Zhang QY, Zhang Y, Liu JJ, Rui JA, Wei X, Ye DX | display-authors = 6 | title = Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma | journal = Oncogene | volume = 22 | issue = 32 | pages = 5060–5069 | date = August 2003 | pmid = 12902989 | doi = 10.1038/sj.onc.1206832 | doi-access = free }}
• {{cite journal | vauthors = Liu XR, Zhou RL, Zhang QY, Zhang Y, Jin YY, Lin M, Rui JA, Ye DX | display-authors = 6 | title = Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma | journal = World Journal of Gastroenterology | volume = 10 | issue = 11 | pages = 1555–1559 | date = June 2004 | pmid = 15162524 | pmc = 4572753 | doi = 10.3748/wjg.v10.i11.1555 | doi-access = free }}
• {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | display-authors = 6 | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–2144 | date = October 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
• {{cite journal | vauthors = Kasper G, Vogel A, Klaman I, Gröne J, Petersen I, Weber B, Castaños-Vélez E, Staub E, Mennerich D | display-authors = 6 | title = The human LAPTM4b transcript is upregulated in various types of solid tumours and seems to play a dual functional role during tumour progression | journal = Cancer Letters | volume = 224 | issue = 1 | pages = 93–103 | date = June 2005 | pmid = 15911104 | doi = 10.1016/j.canlet.2004.10.004 }}
• {{cite journal | vauthors = Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T | display-authors = 6 | title = Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries | journal = DNA Research | volume = 12 | issue = 2 | pages = 117–126 | year = 2007 | pmid = 16303743 | doi = 10.1093/dnares/12.2.117 | doi-access = free }}
• {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | display-authors = 6 | title = The LIFEdb database in 2006 | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D415–D418 | date = January 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
• {{cite journal | vauthors = Maeda K, Horikoshi T, Nakashima E, Miyamoto Y, Mabuchi A, Ikegawa S | title = MATN and LAPTM are parts of larger transcription units produced by intergenic splicing: intergenic splicing may be a common phenomenon | journal = DNA Research | volume = 12 | issue = 5 | pages = 365–372 | year = 2007 | pmid = 16769693 | doi = 10.1093/dnares/dsi017 | doi-access = free }}
• {{cite journal | vauthors = Liu Y, Zhang QY, Qian N, Zhou RL | title = Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer | journal = Annals of Oncology | volume = 18 | issue = 2 | pages = 311–316 | date = February 2007 | pmid = 17074969 | doi = 10.1093/annonc/mdl394 | doi-access = free }}

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