Open AccessLow levels of AMPK promote epithelial‐mesenchymal transition in lung cancer primarily through HDAC4‐ and HDAC5‐mediated metabolic reprogramming
Author(s) -
Feng Shoujie,
Zhang Li,
Liu Xiucheng,
Li Guangbin,
Zhang Biao,
Wang Ziwen,
Zhang Hao,
Ma Haitao
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15410
Subject(s) - ampk , epithelial–mesenchymal transition , cancer research , reprogramming , metastasis , warburg effect , microbiology and biotechnology , lung cancer , biology , cancer cell , protein kinase a , glycolysis , endocrinology , kinase , medicine , cancer , cell , metabolism , biochemistry
AMP‐activated protein kinase (AMPK) serves as a “supermetabolic regulator” that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non–small‐cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up‐regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK‐induced metabolism can promote epithelial‐mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.