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Open AccessArticle

HSF1 Regulates Mevalonate and Cholesterol Biosynthesis Pathways

1
Department of Applied Life Sciences, Graduate School of Konkuk University, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea
2
Diabetes and Bio-Research Center, Konkuk University, Chungju 27478, Chungbuk, Korea
3
Department of Biomedical Chemistry, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea
4
Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju 27478, Chungbuk, Korea
5
Research Institute, National Cancer Center, Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea
6
College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(9), 1363; https://doi.org/10.3390/cancers11091363
Received: 20 August 2019 / Revised: 8 September 2019 / Accepted: 11 September 2019 / Published: 13 September 2019
Heat shock factor 1 (HSF1) is an essential transcription factor in cellular adaptation to various stresses such as heat, proteotoxic stress, metabolic stress, reactive oxygen species, and heavy metals. HSF1 promotes cancer development and progression, and increased HSF1 levels are frequently observed in multiple types of cancers. Increased activity in the mevalonate and cholesterol biosynthesis pathways, which are very important for cancer growth and progression, is observed in various cancers. However, the functional role of HSF1 in the mevalonate and cholesterol biosynthesis pathways has not yet been investigated. Here, we demonstrated that the activation of RAS-MAPK signaling through the overexpression of H-RasV12 increased HSF1 expression and the cholesterol biosynthesis pathway. In addition, the activation of HSF1 was also found to increase cholesterol biosynthesis. Inversely, the suppression of HSF1 by the pharmacological inhibitor KRIBB11 and short-hairpin RNA (shRNA) reversed H-RasV12-induced cholesterol biosynthesis. From the standpoint of therapeutic applications for hepatocellular carcinoma (HCC) treatment, HSF1 inhibition was shown to sensitize the antiproliferative effects of simvastatin in HCC cells. Overall, our findings demonstrate that HSF1 is a potential target for statin-based HCC treatment. View Full-Text
Keywords: heat shock factor 1; cholesterol; KRIBB11; simvastatin; hepatocellular carcinoma heat shock factor 1; cholesterol; KRIBB11; simvastatin; hepatocellular carcinoma
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Kang, H.; Oh, T.; Bahk, Y.Y.; Kim, G.-H.; Kan, S.-Y.; Shin, D.H.; Kim, J.H.; Lim, J.-H. HSF1 Regulates Mevalonate and Cholesterol Biosynthesis Pathways. Cancers 2019, 11, 1363.

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