Oncotarget

Research Papers:

MAEL contributes to gastric cancer progression by promoting ILKAP degradation

Xing Zhang, Yichong Ning, Yuzhong Xiao, Huaxin Duan, Guifang Qu, Xin Liu, Yan Du, Dejian Jiang and Jianlin Zhou _

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Oncotarget. 2017; 8:113331-113344. https://doi.org/10.18632/oncotarget.22970

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Abstract

Xing Zhang1,*, Yichong Ning1,*, Yuzhong Xiao2,*, Huaxin Duan3, Guifang Qu3, Xin Liu1, Yan Du1, Dejian Jiang4 and Jianlin Zhou1

1Key Laboratory of Protein Chemistry and Developmental Biology of The Ministry of Education, College of Life Science, Hunan Normal University, Changsha 410081, Hunan, China

2College of Biology, Hunan University, Changsha 410082, Hunan, China

3The First Affiliated Hospital, Hunan Normal University, Changsha 410005, Hunan, China

4Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha 410331, Hunan, China

*These authors contributed equally to this work

Correspondence to:

Jianlin Zhou, email: jlzhou@hunnu.edu.cn

Keywords: MAEL; gastric cancer; ILKAP; CHK1; p38 MAPK

Received: July 06, 2017     Accepted: November 13, 2017     Published: December 06, 2017

ABSTRACT

The cancer-testis gene MAEL 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 MAEL 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 MAEL expression may serve as a prognostic marker for GC patients (overall survival: hazard ratio [HR] = 1.54, p = 1.2E-4; first progression: HR = 1.51, p = 8.7E-4). In vitro and in vivo experiments demonstrated that silencing MAEL expression in the GC cell lines HGC-27 and AGS inhibits proliferation, colony formation, migration, invasion and growth of xenograft tumors, whereas MAEL 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 ILKAP overexpression reversed the oncogenic effects of MAEL in vitro and in vivo. Taken together, these results indicate that MAEL exerts its oncogenic function by promoting ILKAP degradation in the GC.


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