Analyse protéomique de la sénescence induite par la chimiothérapie dans le cancer de l'ovaire
Patients treated for an advanced ovarian clear cell carcinoma (OCCC) have a poor 5-year survival rate due to treatment resistance. Since 30 years, the therapeutic strategy consists of a combination of carboplatin and paclitaxel (CP). It is of the upmost urgency to find new treatments against this cancer. We studied the impact of CP treatment on an OCCC cell line and observed that it induced a senescence state in the cells. Senescent cells do not proliferate anymore but have a huge impact on their microenvironment by secreting a complex mix of molecules. We need to know better the characteristics of chemotherapy-induced senescent cells to be able to target them with new treatments. Consequently, we studied the cell surface proteins of senescent cells with a cutting-edge proteomic method. We found that the protein DNAJC5 was upregulated at the cell surface of senescent cells. This chaperone is implicated in exo- and endocytosis mechanisms, as well as in a non-conventional secretion pathway. We wanted to know if this pathway was activated in senescent cells and we studied the impact of DNAJC5 inhibition on the cell proteotoxicity and on senescence establishment. Our first results suggest that DNAJC5 would have a role in senescence, which has never been observed. In the future, this discovery could contribute to the development of new treatments for the COCC.
surfaceome DNAJC5 Ovarian cancer non-conventional secretion pathways