Modulation of claudin-1 expression by ∆2-TGZ in triple negative breast cancer cells is correlated to apoptosis
Résumé
Breast cancer represents the first lethal malignancy across the world in women. Innate and acquired resistances are the leading causes of therapeutic failure. Furthermore, 76% of triple negative tumors (ER-, PR- and HER2-) do not express any more claudin 1, a major constituent of tight junctions. Patients with these “claudin 1-low” triple negative tumors present a high relapse incidence. A major challenge in oncology is the development of innovative therapies for these poor prognosis tumors. In this context, our laboratory synthetized a promising compound derived from troglitazone (TGZ), Δ2-TGZ, which presents a higher antiproliferative activity and a lower hepatic toxicity than its parental compound. In this study, we showed that 1) Δ2-TGZ induces claudin 1 expression and apoptosis in triple negative breast cancer cells but not in non-tumorigenic mammary cells; 2) Claudin 1 overexpression leads to a pro-apoptotic effect in triple negative MDA-MB-231 and Hs578T cells and 3) Claudin 1 knockdown prevents Δ2-TGZ-induced apoptotic effect in triple negative MDA-MB-231 cells. In fine, our study suggests that the strategy of claudin-1 re-expression could be a promising therapeutic option for the aggressive “claudin 1-low” triple negative tumors.