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La claudine 1 : une piste pour sensibiliser les cellules cancéreuses mammaires triple-négatives à la chimiothérapie

Abstract : Claudin-1: a way to sensitize triple-negative breast cancer cells to chemotherapyTriple-negative breast cancer (TNBC) represents 20% of breast tumors and their treatment is a major issue in oncology because only few effective targeted therapies are currently available to treat them. Among TNBCs, 77% of them do not express the claudin-1 (a tight junction protein) and are referred as "claudin-1-low" tumor. These tumors have a higher recurrence risk, higher metastatic capacities, and bigger resistance to chemotherapy. Although claudin-1 role in breast cancer is not clearly defined, several studies suggest that it may be a tumor suppressor. Recent data from my laboratory confirm this hypothesis since claudin-1 expression induces apoptosis of two TNBC “claudin-1-low” cell lines: MDA-MB- 231 and Hs578T. The works established during my thesis demonstrate that the HCC1806 TNBC cell line, which expresses the claudin-1, is more sensitive than the MDA-MB-231 and Hs578T cells to three chemotherapy agents commonly used in breast tumors treatment: 5- FU, paclitaxel and doxorubicin. The results obtained also underline the claudin-1 involvement in this sensitivity, and that its expression sensitizes “claudin-1-low” TNBC cells to chemotherapeutic agents. In order to understand its involvement in this process, the search for its protein partners, as well as the identification of key regulators of its expression have been initiated. All the work carried out during this thesis could allow the claudin-1 establishment as a prognostic chemotherapy response marker. In the futur, this work could also guide the search for new therapeutic targets allowing the claudin-1 expression in TNBC and thus increase their sensitivity to chemotherapy.
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Submitted on : Tuesday, October 4, 2022 - 4:13:15 PM
Last modification on : Sunday, November 27, 2022 - 5:28:08 AM


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Marine Lemesle. La claudine 1 : une piste pour sensibiliser les cellules cancéreuses mammaires triple-négatives à la chimiothérapie. Cancer. Université de Lorraine, 2022. Français. ⟨NNT : 2022LORR0061⟩. ⟨tel-03797161⟩



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