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

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dc.contributor.ORCID0000-0002-7829-1480 (Kim, J-w)en_US
dc.contributor.authorJeon, J. Y.en_US
dc.contributor.authorLee, M.en_US
dc.contributor.authorWhang, S. H.en_US
dc.contributor.authorKim, Jung-whanen_US
dc.contributor.authorCho, A.en_US
dc.contributor.authorYun, M.en_US
dc.contributor.utdAuthorKim, Jung-whanen_US
dc.date.accessioned2018-10-22T20:05:59Z
dc.date.available2018-10-22T20:05:59Z
dc.date.created2018-01-19en_US
dc.date.issued2018-10-22
dc.description.abstractAltered 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.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorship"This work was supported by the National Research Foundation of Korea grants funded by the Korean government (MSIP) (NRF-2011-0030086 and NRF- 2016R1E1A1A01943303), and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning (2012R1A1A3008042)."en_US
dc.identifier.bibliographicCitationJeon, J. Y., M. Lee, S. H. Whang, J. -W Kim, et al. 2018. "Regulation of acetate utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC)." Oncology Research 26(1), doi: 10.3727/096504017X14902648894463en_US
dc.identifier.issn0965-0407en_US
dc.identifier.issue1en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6234
dc.identifier.volume26en_US
dc.language.isoenen_US
dc.publisherCognizant Communication Corporationen_US
dc.relation.urihttp://dx.doi.org/10.3727/096504017X14902648894463
dc.rights"Oncology Research is an open access journal and follows rules governed by open access publications."en_US
dc.rights©2018 Cognizant, LLCen_US
dc.sourceOncology Research
dc.subjectCarcinoma, Hepatocellularen_US
dc.subjectMonocarboxylic Acid Transportersen_US
dc.subjectPositron-Emission Tomographyen_US
dc.subjectAcetic aciden_US
dc.subjectSmall interfering RNAen_US
dc.subjectCell proliferationen_US
dc.subjectGene Knockdown Techniquesen_US
dc.subjectGene targetingen_US
dc.subjectHumansen_US
dc.subjectLipogenesisen_US
dc.subjectOxygen consumption (Physiology)en_US
dc.subjectPhosphorylationen_US
dc.subjectLiver--Canceren_US
dc.subjectTomography, Emissionen_US
dc.subjectOxygen Consumptionen_US
dc.titleRegulation of Acetate Utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC)en_US
dc.type.genrearticleen_US

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