Cancer du sein et micro-environnement tumoral: rôle de la protéase ...

ABSTRACTThe aspartic protease cathepsin-D (cath-D) is overexpressed by human epithelialbreast cancer cells and is closely correlated with poor prognosis in breast cancer.Adipocyte is one of the most prominent cell types in the tumor-microenvironment ofbreast cancers and clinical studies pointed out that obesity increases the incidence ofbreast cancer. Here, we provide the first evidence that cath-D expression is upregulatedin adipose tissue of obese human as well as in adipocytes of obeseC57BI6/J mouse model. Cath-D expression is also increased during human andmouse adipocyte differentiation. We demonstrate that cath-D silencing in NIH-3T3F442A murine preadipocytes significantly inhibits the expression of PPARg, HSLand aP2 adipocyte differentiation markers after adipogenesis induction, and leads tolipid-depleted cells. This study highlights the key role of cath-D in the control ofadipogenesis, and suggests that this protease may be a novel target in obesity.Since cath-D is implicated in breast cancer progression, we propose that cath-D mayrepresent a molecular link between cancer and obesity.2