MAEL contributes to gastric cancer progression by promoting ILKAP degradation

Abstract

The cancer-testis gene <i>MAEL</i> is involved in the development and progression of bladder, liver and colorectal cancers. However, its role in other cancers is unclear. By systematically analyzing transcriptomics and genomics data from various cancer databases, we identified that the <i>MAEL</i> gene is aberrantly elevated in gastric cancer (GC) tissues and that its expression is strongly negatively correlated with DNA methylation (Pearson's correlation coefficient = -0.675). Survival analysis revealed that <i>MAEL</i> expression may serve as a prognostic marker for GC patients (overall survival: hazard ratio [HR] = 1.54, <i>p</i> = 1.2E-4; first progression: HR = 1.51, <i>p</i> = 8.7E-4). <i>In vitro</i> and <i>in vivo</i> experiments demonstrated that silencing <i>MAEL</i> expression in the GC cell lines HGC-27 and AGS inhibits proliferation, colony formation, migration, invasion and growth of xenograft tumors, whereas <i>MAEL</i> overexpression exerts the opposite effects in the normal gastric cell line GES-1. Mechanistically, MAEL promotes the lysosome-dependent degradation of the protein phosphatase ILKAP, leading to increased phosphorylation of its substrates (p38, CHK1 and RSK2). Moreover, adenovirus-mediated <i>ILKAP</i> overexpression reversed the oncogenic effects of <i>MAEL in vitro</i> and <i>in vivo.</i> Taken together, these results indicate that <i>MAEL</i> exerts its oncogenic function by promoting ILKAP degradation in the GC.