ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate

Author:

Yang Yanting1,Zhang Zhenxi1,Li Wei1,Li Li1,Zhou Ying2,Du Wenjing12

Affiliation:

1. State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Cell Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China

2. Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan 030606, China

Abstract

Cancer metastasis is still a major challenge in clinical cancer treatment. The migration and invasion of cancer cells into surrounding tissues and blood vessels is the primary step in cancer metastasis. However, the underlying mechanism of regulating cell migration and invasion are not fully understood. Here, we show the role of malic enzyme 2 (ME2) in promoting human liver cancer cell lines SK-Hep1 and Huh7 cells migration and invasion. Depletion of ME2 reduces cell migration and invasion, whereas overexpression of ME2 increases cell migration and invasion. Mechanistically, ME2 promotes the production of pyruvate, which directly binds to β-catenin and increases β-catenin protein levels. Notably, pyruvate treatment restores cell migration and invasion of ME2-depleted cells. Our findings provide a mechanistic understanding of the link between ME2 and cell migration and invasion.

Funder

National Key Research and Development Program of China

CAMS Innovation Fund for Medical Sciences

Haihe Laboratory of Cell Ecosystem Innovation Fund

CAMS Basic Research Fund

State Key Laboratory Special Fund

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism

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