Background: Diet and obesity are considered important risk factors for cancer development. Many studies have suggested an important role for several dietary nutrients in the progression and development of breast cancer. However, very few investigations have specifically addressed the role of cholesterol as an important factor contributing to breast cancer progression.
In recent studies, we have examined the role of cholesterol in the regulation of tumor progression in a mouse model of mammary tumor formation. Our results suggest that cholesterol accelerates and enhances tumor formation. In agreement with this finding, we have shown that tumors were more aggressive and tumor angiogenesis was enhanced in this context. In addition, we have also examined in a xenograft tumor model the role of a lipoprotein receptor, SR-BI, responsible for cellular cholesterol uptake. We found that reducing cellular cholesterol levels by reducing SR-BI protein levels was associated with reduced tumor formation as a consequence of reduced cellular proliferation, migration, and increased cellular apoptosis. Our data show that various signaling pathways involved in these cellular functions are regulated by SR-BI and cholesterol.
The recognition of cholesterol as a factor contributing to breast cancer development identifies cholesterol and participants in its metabolism as novel targets for cancer therapy.

Relevant Publications:

1. Llaverias G, C Danilo, I Mercier, K Daumer, F Capozza, TM Williams, F Sotgia, MP Lisanti, PG Frank. Role of Cholesterol in the Development and Progression of Breast Cancer. Am J Pathol. 2011. 178(1):402-412.
2. Danilo C & PG Frank. Cholesterol and Breast Cancer Development. Curr Opin Pharmacol. 2012. 12: 677–682.
3. Danilo C, JL Gutierrez-Pajares, MA Mainieri, I Mercier, MP Lisanti, and PG Frank. SR-BI Regulates Cellular Cholesterol Metabolism and Cell Signaling Associated with Breast Cancer Development. Breast Cancer Res. 2013. 15(5):R87.

Invitation: Laurent Lagrost UMR866

Le séminaire aura lieu à la Faculté de Médecine Dijon, Amphi Courtois à 14h00

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