title: Down-regulation of LAPTM5 in human cancer cells.
abstract: Lysosomal-associated protein multispanning transmembrane 5 (LAPTM5) is a membrane protein that localizes to intracellular vesicles. It has been previously demonstrated that LAPTM5 expression level is decreased in neuroblastoma (NB) cells, and excessive accumulation of LAPTM5 was shown to induce lysosomal cell death in these cells. However, the pathological expression and role of LAPTM5 in other types of human cancers are largely unknown. Here, we found that LAPTM5 mRNA level is frequently decreased in various cancer cell lines, and its low expression in patients with esophageal squamous cell carcinoma (ESCC) and non-small cell lung cancer (NSCLC) was significantly correlated with poor prognosis. Furthermore, we showed that overexpression of LAPTM5 in several cancer cells induces lysosomal cell death due to lysosomal destabilization, indicated by leakage of lysosomal cathepsin D into the cytosol as well as impairment of autophagy. These findings suggest that the inactivation of LAPTM5 may contribute to tumorigenesis in a subset of human cancers.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Michelle
authors.initials: M
authors.lastname: Nuylan
authors.affiliation: Department of Esophageal and General Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Genome Medicine, Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan.|Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.|Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C100848:LAPTM5 protein, human
keywords: ESCC; LAPTM5; cell death; lysosomes; tumor suppressor genes