CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy.

Fiche publication

Date publication

octobre 2022

Journal

Cancers

Auteurs

Membres identifiés du Cancéropôle Est :
Dr ALPY Fabien , Dr GRILLIER-VUISSOZ Isabelle , Dr KUNTZ Sandra , Dr TOMASETTO Catherine

Tous les auteurs :
Lemesle M, Geoffroy M, Alpy F, Tomasetto CL, Kuntz S, Grillier-Vuissoz I

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36291810

Résumé

Triple-negative breast cancer (TNBC) is an aggressive subtype that constitutes 15-20% of breast cancer cases worldwide. Current therapies often evolve into chemoresistance and lead to treatment failure. About 77% of the TNBC lacks claudin-1 (CLDN1) expression, a major tight junction component, and this absence is correlated with poorer prognostic. Little is known about CLDN1 role on the chemosensitivity of breast cancer. Our clinical data analysis reveals that CLDN1 low expression is correlated to a poor prognostic in TNBC patients. Next, the sensitivity of various TNBC "claudin-1-high" or "claudin-1-low" cells to three compounds belonging to the main class of chemotherapeutic agents commonly used for the treatment of TNBC patients: 5-fluorouracil (5-FU), paclitaxel (PTX) and doxorubicin (DOX). Using RNA interference and stable overexpressing models, we demonstrated that CLDN1 expression increased the sensitivity of TNBC cell lines to these chemotherapeutic agents. Taken together, our data established the important role of CLDN1 in TNBC cells chemosensitivity and supported the hypothesis that CLDN1 could be a chemotherapy response predictive marker for TNBC patients. This study could allow new treatment protocols creation aimed to induce CLDN1 expression in TNBCs to increase their sensitivity to chemotherapy.