Maternal embryonic leucine zipper kinase enhances gastric cancer progression via the FAK/Paxillin pathway

被引：78

作者：

Du, Tao ^{[1
]}

Qu, Ying ^{[1
]}

Li, Jianfang ^{[1
]}

Li, Hao ^{[1
]}

Su, Liping ^{[1
]}

Zhou, Quan ^{[1
]}

Yan, Min ^{[1
]}

Li, Chen ^{[1
]}

Zhu, Zhenggang ^{[1
]}

Liu, Bingya ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Inst Digest Surg, Shanghai Key Lab Gastr Neoplasms,Ruijin Hosp, Sch Med,Dept Surg, Shanghai 200025, Peoples R China

来源：

MOLECULAR CANCER | 2014年 / 13卷

基金：

中国国家自然科学基金;

关键词：

MELK; Gastric cancer; Tumor migration; Tumor invasion; FAK; Paxillin; PROTEIN-KINASE; MELK; ADHESION; PHOSPHORYLATION; CELLS; PROLIFERATION; PAXILLIN; INVOLVEMENT; METASTASIS; INVASION;

D O I：

10.1186/1476-4598-13-100

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Elevated MELK expression is featured in multiple tumors and correlated with tumorigenesis and tumor development. This study is aimed to investigate the mechanisms of MELK-mediated development of gastric cancer. Methods: MELK expression levels in human gastric cancer were determined by quantitative-PCR and immunohistochemistry. The effect of MELK on cell activity was explored by knockdown and overexpression experiments. Cell growth was measured using the CCK-8 assay. Apoptosis and cell cycle distributions were analyzed by flow cytometry. Migration and invasion were tested using a transwell migration assay. Cytoskeletal changes were analyzed by immunofluorescence. To explore the molecular mechanism and effect of MELK on migration and invasion, Western blotting was used to analyze the FAK/Paxillin pathway and pull down assays for the activity of small Rho GTPases. In vivo tumorigenicity and peritoneal metastasis experiments were performed by tumor cell engraftment into nude mice. Results: MELK mRNA and protein expression were both elevated in human gastric cancer, and this was associated with chemoresistance to 5-fluorouracil (5-FU). Knockdown of MELK significantly suppressed cell proliferation, migration and invasion of gastric cancer both in vitro and in vivo, decreased the percentages of cells in the G1/G0 phase and increased those in the G2/M and S phases. Moreover, knockdown of MELK decreased the amount of actin stress fibers and inhibited RhoA activity. Finally, knockdown of MELK decreased the phosphorylation of the FAK and paxillin, and prevented gastrin-stimulated FAK/paxillin phosphorylation. By contrast, MELK overexpression had the opposite effect. Conclusions: MELK promotes cell migration and invasion via the FAK/Paxillin pathway, and plays an important role in the occurrence and development of gastric cancer. MELK may be a potential target for treatment against gastric cancer.

引用

页数：14

共 47 条

[1] M-phase MELK activity is regulated by MPF and MAPK [J].