Cancers, Vol. 11, Pages 1363: HSF1 Regulates Mevalonate and Cholesterol Biosynthesis Pathways

Cancers, Vol. 11, Pages 1363: HSF1 Regulates Mevalonate and Cholesterol Biosynthesis Pathways Cancers doi: 10.3390/cancers11091363 Authors: Hyeji Kang Taerim Oh Young Yil Bahk Geon-Hee Kim Sang-Yeon Kan Dong Hoon Shin Ji Hyung Kim Ji-Hong Lim 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. O...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research