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Regulation of Acetate Utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC).

 Jeon, Jeong Yong  ;  Lee, Misu  ;  Whang, Sang Hyun  ;  Kim, Jung-Whan  ;  Cho, Arthur  ;  Yun, Mijin 
 ONCOLOGY RESEARCH, Vol.26(1) : 71-81, 2018 
Journal Title
Issue Date
Acetates/metabolism* ; Carbon Radioisotopes ; Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Energy Metabolism/physiology* ; Humans ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/metabolism* ; Monocarboxylic Acid Transporters/metabolism* ; Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; Retrospective Studies ; Symporters/metabolism*
Hepatocellular carcinoma (HCC) ; Monocarboxylate transporter (MCT) ; Positron emission tomography/computed tomography (PET/CT) ; [11C]Acetate uptake
Altered energy metabolism is a biochemical fingerprint of cancer cells. Hepatocellular carcinoma (HCC) shows reciprocal [18F]fluorodeoxyglucose (FDG) and [11C]acetate uptake, as revealed by positron emission tomography/computed tomography (PET/CT). Previous studies have focused on the role of FDG uptake in cancer cells. In this study, we evaluated the mechanism and roles of [11C]acetate uptake in human HCCs and cell lines. The expression of monocarboxylate transporters (MCTs) was assessed to determine the transporters of [11C]acetate uptake in HCC cell lines and human HCCs with different [11C]acetate uptake. Using two representative cell lines with widely different [11C]acetate uptake (HepG2 for high uptake and Hep3B for low uptake), changes in [11C]acetate uptake were measured after treatment with an MCT1 inhibitor or MCT1-targeted siRNA. To verify the roles of MCT1 in cells, oxygen consumption rate and the amount of lipid synthesis were measured. HepG2 cells with high [11C]acetate uptake showed higher MCT1 expression than other HCC cell lines with low [11C]acetate uptake. MCT1 expression was elevated in human HCCs with high [11C]acetate uptake compared to those with low [11C]acetate uptake. After blocking MCT1 with AR-C155858 or MCT1 knockdown, [11C]acetate uptake in HepG2 cells was significantly reduced. Additionally, inhibition of MCT1 suppressed mitochondrial oxidative phosphorylation, lipid synthesis, and cellular proliferation in HCC cells with high [11C]acetate uptake. MCT1 may be a new therapeutic target for acetate-dependent HCCs with high [11C]acetate uptake, which can be selected by [11C]acetate PET/CT imaging in clinical practice.
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1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Jeon, Jeong Yong(전정용)
Cho, Arthur Eung Hyuck(조응혁) ORCID logo https://orcid.org/0000-0001-8670-2473
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