Research Papers:

Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in gastric cancer

Shen Li, Ziyu Li, Ting Guo, Xiao-Fang Xing, Xiaojing Cheng, Hong Du, Xian-Zi Wen and Jia-Fu Ji _

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Oncotarget. 2016; 7:6266-6280. https://doi.org/10.18632/oncotarget.6673

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Shen Li1,2, Ziyu Li2, Ting Guo1, Xiao-Fang Xing1, Xiaojing Cheng1, Hong Du1, Xian-Zi Wen1, Jia-Fu Ji1,2

1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China

2Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China

Correspondence to:

Xian-Zi Wen, e-mail: [email protected]

Jia-Fu Ji, e-mail: [email protected]

Keywords: MELK, gastric cancer, prognosis, metastasis, PDX

Received: July 02, 2015     Accepted: December 07, 2015     Published: December 19, 2015


Maternal embryonic leucine zipper kinase (MELK) is upregulated in a variety of human tumors, and is considered an attractive molecular target for cancer treatment. We characterized the expression of MELK in gastric cancer (GC) and measured the effects of reducing MELK mRNA levels and protein activity on GC growth. MELK was frequently overexpressed in primary GCs, and higher MELK levels correlated with worse clinical outcomes. Reducing MELK expression or inhibiting kinase activity resulted in growth inhibition, G2/M arrest, apoptosis and suppression of invasive capability of GC cells in vitro and in vivo. MELK knockdown led to alteration of epithelial mesenchymal transition (EMT)-associated proteins. Furthermore, targeting treatment with OTSSP167 in GC patient-derived xenograft (PDX) models had anticancer effects. Thus, MELK promotes cell growth and invasiveness by inhibiting apoptosis and promoting G2/M transition and EMT in GC. These results suggest that MELK may be a promising target for GC treatment.

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