Proteases hydrolyse peptide bounds in proteins, representing an important and irreversible post-translational modification. These enzymes are implicated in normal physiological processes but deregulations of their expression in pathologies such cancer have profound consequences. The main goal of the team is to dissect out the roles and action mechanisms of the lysosomal aspartic protease cathepsin D (cath-D) in cancer through several important biological processes such as proliferation, invasion, autophagy and apoptosis.
The lysosomal aspartic protease cath-D is an independent marker of poor prognosis in breast cancer being correlated with the incidence of clinical metastasis and stimulates cancer cell proliferation and metastasis. Our recent studies demonstrate that cath-D can induce fibroblast invasive growth via a paracrine loop, suggesting a key role for it in tumor micro-environment. A mutated D231N cath-D, devoid of catalytic activity, still proved mitogenic, indicating a possible action of cath-D by protein-protein interaction. Cath-D is successively processed into different intermediate species by complex mechanisms involving the cysteine proteases cathepsins B and L. Cath-D overexpressed by cancer cells enhances apoptosis-dependent chemo-sensitivity.
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Masson O, Chavey C, Dray C, Meulle A, Daviaud D, Quilliot D, Muller C, Valet P, Liaudet-Coopman E. LRP1 receptor controls adipogenesis and is up-regulated in human and mouse obese adipose tissue. PLoS One. 2009 Oct 12;4(10):e7422.
Pattingre S, Bauvy C, Carpentier S, Levade T, Levine B, Codogno P. Role of JNK1 dependent Bcl-2 phosphorylation in ceramide-induced macroautophagy. J Biol Chem. 2009. 284:2719-28.
Beaujouin M, Liaudet-Coopman E. Cathepsin Doverexpressed by cancer cells can enhance apoptosis-dependent chemo-sensitivity independently of its catalyticactivity. Adv Exp Med Biol 2008; 617: 453-461.
Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P. Regulation of macroautophagy by TOR and Beclin 1 complexes. Biochimie. 2008. 90:313-23.
