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. 2021 Jun 17;11:12763. doi: 10.1038/s41598-021-91928-3

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Dual inhibition of HMGCR in TGF-β-induced epithelial cancer cells. Following microenvironment-induced phenotypic state switch in epithelial cancer cells the dual inhibition of HMGCR, by downregulation of its expression (by siRNA or Cmpd81) and its enzymatic activity (by statins) leads to reduced cholesterol levels and reduced synthesis of the mevalonate pathway’s intermediate metabolites that are required for prenylation of signaling proteins. This dual treatment regimen may also reduce the metastatic competence of emerging (micro)tumors to a greater extent than atorvastatin treatment alone¹⁹.