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Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect

Authors Tian H, Zhu X, Lv Y, Jiao Y, Wang G

Received 14 April 2020

Accepted for publication 30 June 2020

Published 17 July 2020 Volume 2020:12 Pages 5957—5974

DOI https://doi.org/10.2147/CMAR.S258196

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Seema Singh


Huining Tian,1 Xiaoyu Zhu,2 You Lv,1 Yan Jiao,3 Guixia Wang1

1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 2Department of Nephrology, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China

Correspondence: Guixia Wang
Department of Endocrinology and Metabolism, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun 130021, Jilin, People’s Republic of China
Tel +86 158 0438 1103
Fax +86 431 8878 6259
Email gwang168@jlu.edu.cn
Yan Jiao
Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun 130021, Jilin, People’s Republic of China
Tel/ Fax +86 13843101157
Email lagelangri1@126.com

Abstract: Hepatocellular carcinoma (HCC) is a tumor that exhibits glucometabolic reprogramming, with a high incidence and poor prognosis. Usually, HCC is not discovered until an advanced stage. Sorafenib is almost the only drug that is effective at treating advanced HCC, and promising metabolism-related therapeutic targets of HCC are urgently needed. The “Warburg effect” illustrates that tumor cells tend to choose aerobic glycolysis over oxidative phosphorylation (OXPHOS), which is closely related to the features of the tumor microenvironment (TME). The HCC microenvironment consists of hypoxia, acidosis and immune suppression, and contributes to tumor glycolysis. In turn, the glycolysis of the tumor aggravates hypoxia, acidosis and immune suppression, and leads to tumor proliferation, angiogenesis, epithelial–mesenchymal transition (EMT), invasion and metastasis. In 2017, a mechanism underlying the effects of gluconeogenesis on inhibiting glycolysis and blockading HCC progression was proposed. Treating HCC by increasing gluconeogenesis has attracted increasing attention from scientists, but few articles have summarized it. In this review, we discuss the mechanisms associated with the TME, glycolysis and gluconeogenesis and the current treatments for HCC. We believe that a treatment combination of sorafenib with TME improvement and/or anti-Warburg therapies will set the trend of advanced HCC therapy in the future.

Keywords: hepatocellular carcinoma, tumor microenvironment, glycolysis, gluconeogenesis, Warburg effect

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