New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration.

Brindisi, M ORCID: https://orcid.org/0000-0002-5022-9642, Frattaruolo, L ORCID: https://orcid.org/0000-0002-7018-8454, Fiorillo, M ORCID: https://orcid.org/0000-0002-8055-3259, Dolce, V ORCID: https://orcid.org/0000-0003-2966-4866, Sotgia, F ORCID: https://orcid.org/0000-0003-2826-4529, Lisanti, MP ORCID: https://orcid.org/0000-0003-2034-1382 and Cappello, AR ORCID: https://orcid.org/0000-0001-7824-3561 2022, 'New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration.' , The FEBS journal .

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Abstract

Breast cancer remains the greatest cause of cancer-related death in women worldwide. Its aggressiveness and progression derive from intricate processes that occur simultaneously both within the tumour itself and in the neighbouring cells that make up its microenvironment. The aim of the present work was firstly to study how elevated cholesterol levels increase tumour aggressiveness. Herein, we demonstrate that cholesterol, by activating ERRα pathway, promotes epithelium-mesenchymal transition (EMT) in breast cancer cells (MCF-7 and MDA-MB-231) as well as the release of pro-inflammatory factors able to orchestrate the tumour microenvironment. A further objective of this work was to study the close symbiosis between tumour cells and the microenvironment. Our results allow us to highlight, for the first time, that breast cancer cells exposed to high cholesterol levels promote (a) greater macrophages infiltration with induction of an M2 phenotype, (b) angiogenesis and endothelial branching, as well as (c) a cancer-associated fibroblasts (CAFs) phenotype. The effects observed could be due to direct activation of the ERRα pathway by high cholesterol levels, since the simultaneous inhibition of this pathway subverts such effects. Overall, these findings enable us to identify the cholesterol-ERRα synergy as an interesting target for breast cancer treatment. [Abstract copyright: © 2022 Federation of European Biochemical Societies.]

Item Type: Article
Additional Information: This is the accepted version of the following article: Brindisi, M., Frattaruolo, L., Fiorillo, M., Dolce, V., Sotgia, F., Lisanti, M.P. and Cappello, A.R. (2022), New insights into cholesterol-mediated ERRα activation in breast cancer progression and pro-tumoral microenvironment orchestration. FEBS J. https://doi.org/10.1111/febs.16651, which has been published in final form at https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16651
Schools: Schools > School of Computing, Science and Engineering
Journal or Publication Title: The FEBS journal
Publisher: Wiley
ISSN: 1742-464X
Funders: Regione Calabria
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 16 Nov 2022 09:13
Last Modified: 16 Nov 2022 09:15
URI: https://usir.salford.ac.uk/id/eprint/65398

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