Jump to content

LAPTM4B

From Wikipedia, the free encyclopedia
LAPTM4B
Identifiers
AliasesLAPTM4B, LAPTM4beta, LC27, lysosomal protein transmembrane 4 beta
External IDsOMIM: 613296; MGI: 1890494; HomoloGene: 10182; GeneCards: LAPTM4B; OMA:LAPTM4B - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_018407

NM_033521

RefSeq (protein)

NP_060877

NP_277056

Location (UCSC)Chr 8: 97.78 – 97.85 MbChr 15: 34.24 – 34.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Lysosomal-associated transmembrane protein 4B is a protein that in humans is encoded by the LAPTM4B gene.[5]

LAPTM4B protein contains a lysosome localization motif and localizes on late endosomes and lysosomes.

Clinical significance

[edit]

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.[6]

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.[7] 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.[6]

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.[8] 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.[9] LAPTM4B selectively interacts with inactive EGFR, which is markedly promoted by serum starvation.[9] 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

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000104341Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022257Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: LAPTM4B lysosomal associated protein transmembrane 4 beta".
  6. ^ a b Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, et al. (February 2010). "Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer". Nature Medicine. 16 (2): 214–218. doi:10.1038/nm.2090. PMC 2826790. PMID 20098429.
  7. ^ Li Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, et al. (December 2011). "Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells". Cancer Research. 71 (24): 7481–7489. doi:10.1158/0008-5472.CAN-11-0940. PMC 3261660. PMID 22037872.
  8. ^ Tan X, Sun Y, Thapa N, Liao Y, Hedman AC, Anderson RA (February 2015). "LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation". The EMBO Journal. 34 (4): 475–490. doi:10.15252/embj.201489425. PMC 4331002. PMID 25588945.
  9. ^ a b Tan X, Thapa N, Sun Y, Anderson RA (January 2015). "A kinase-independent role for EGF receptor in autophagy initiation". Cell. 160 (1–2): 145–160. doi:10.1016/j.cell.2014.12.006. PMC 4297316. PMID 25594178.

Further reading

[edit]