title: Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in gastric cancer.
abstract: 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.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.|Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Xing
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Xian-Zi
authors.initials: XZ
authors.lastname: Wen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.|Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Jia-Fu
authors.initials: JF
authors.lastname: Ji
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011247:Pregnancy; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
keywords: MELK; PDX; gastric cancer; metastasis; prognosis