AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis

Hu, Mingyue; Chen, Xiangxu; Ma, Li; Ma, Yu; Li, Yuan; Song, Huihui; Xu, Jiajia; Zhou, Lingna; Li, Xiaoxue; Jiang, Yuhui; Kong, Bo; Huang, Peilin

doi:10.7150/jca.28299

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J Cancer 2019; 10(8):1870-1878. doi:10.7150/jca.28299 This issue Cite

Research Paper

AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis

Mingyue Hu¹, Xiangxu Chen¹, Li Ma¹, Yu Ma¹, Yuan Li¹, Huihui Song¹, Jiajia Xu¹, Lingna Zhou¹, Xiaoxue Li¹, Yuhui Jiang¹, Bo Kong^2,3, Peilin Huang^1✉

1. Medical School of Southeast University, Nanjing 210009, China
2. Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich (TUM), Munich 81675, Germany
3. Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University, Medical School, Nanjing, China.

Citation:

Hu M, Chen X, Ma L, Ma Y, Li Y, Song H, Xu J, Zhou L, Li X, Jiang Y, Kong B, Huang P. AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis. J Cancer 2019; 10(8):1870-1878. doi:10.7150/jca.28299. https://www.jcancer.org/v10p1870.htm

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Abstract

Pancreatic cancer is a highly aggressive tumor characterized by enhanced aerobic glycolysis. AMP-activated protein kinase (AMPK), which is identified as a well-known regulator of glycolysis, plays an essential role in tumorigenesis. In the present study, we aim to explore the function of AMPK in pancreatic cancer cells and attempt to clarify the possible underlying mechanism. The Cancer Genome Atlas (TCGA) data showed that elevated AMPK expression highly correlated with lower median survival time. In an in vitro study, inhibition of AMPK blocked the proliferation, migration, and invasion ability of four cell lines under normoxia and hypoxia. Additionally, AMPK suppression led to cell cycle arrest and remarkably induced apoptosis. Furthermore, the lactic acid content, ATP content, and the glucose consumption rate were significantly reduced in all four cell lines under different conditions, accompanied by down-regulation of glycolytic biomarkers including phosphorylated mammalian target of rapamycin (p-mTOR)/total mTOR (t-mTOR), Pyruvate kinase M2 (Pkm2), and Hexokinase 2 (Hk2). Collectively, our data showed that AMPK activation is highly involved in pancreatic cancer progression and exerts its pro-tumorigenic functions partly by sustaining glycolytic activity. Hence, AMPK is expected to be a potential therapeutic target for pancreatic cancer.

Keywords: pancreatic cancer, aerobic glycolysis, AMPK, mTOR, hypoxia

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APA

Hu, M., Chen, X., Ma, L., Ma, Y., Li, Y., Song, H., Xu, J., Zhou, L., Li, X., Jiang, Y., Kong, B., Huang, P. (2019). AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis. Journal of Cancer, 10(8), 1870-1878. https://doi.org/10.7150/jca.28299.

ACS

Hu, M.; Chen, X.; Ma, L.; Ma, Y.; Li, Y.; Song, H.; Xu, J.; Zhou, L.; Li, X.; Jiang, Y.; Kong, B.; Huang, P. AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis. J. Cancer 2019, 10 (8), 1870-1878. DOI: 10.7150/jca.28299.

NLM

CSE

Hu M, Chen X, Ma L, Ma Y, Li Y, Song H, Xu J, Zhou L, Li X, Jiang Y, Kong B, Huang P. 2019. AMPK Inhibition Suppresses the Malignant Phenotype of Pancreatic Cancer Cells in Part by Attenuating Aerobic Glycolysis. J Cancer. 10(8):1870-1878.

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