MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Xu,Ge; Ge,Yinggang; Tao,Xiaohong; Gao,Qing; Liang,Xiaoyan

doi:10.3892/or.2017.5686

MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition

Authors:
- Ge Xu
- Yinggang Ge
- Xiaohong Tao
- Qing Gao
- Xiaoyan Liang
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Affiliations: Institute of Life Science, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: May 30, 2017 https://doi.org/10.3892/or.2017.5686
Pages: 237-244

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Abstract

Microtubule affinity-regulating kinases (MARKs; MARK1, MARK2, MARK3 and MARK4) act directly downstream of LKB1, the multitasking tumor-suppressor kinase, and thereby mediate its biological effects. Current understanding of the function of MARKs is greatly restricted to regulation of cell polarity. However, whether or how MARKs contribute to cellular growth control remains largely unknown. In the present study, we utilized an inducible lentiviral expression system that allows rapid MARK expression in LKB1-deficient HeLa cells, and characterized additional functions of MARKs: overexpression of MARK2 in HeLa cells resulted in a decrease in cell growth, inhibition of colony formation and arrest in G1 cell cycle phase, with AMPK as the putative downstream effector upregulating the expression of p21 and p16. MARK2 was found to play a role in F-actin reorganization and to contribute to reversal of epithelial‑mesenchymal transition (EMT) as exemplified in the case of HeLa cells that exhibited phenotypic changes, reduced cell migration and invasion. Our findings unveil the coordinated regulation of cell growth and EMT mediated by MARK2, and also provide new insights into the mechanisms underlying the anti-metastatic activity of MARK2.

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