Research Papers:
Down-regulation of LAPTM5 in human cancer cells
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Abstract
Michelle Nuylan1, Tatsuyuki Kawano2, Johji Inazawa1,3,4, Jun Inoue1,4
1Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan
2Department of Esophageal and General Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
3Department of Genome Medicine, Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan
4Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence to:
Jun Inoue, email: [email protected]
Johji Inazawa, email: [email protected]
Keywords: LAPTM5, ESCC, tumor suppressor genes, lysosomes, cell death
Received: November 26, 2015 Accepted: March 18, 2016 Published: April 6, 2016
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.
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