CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy
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 t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/20/5026 |
| _version_ | 1797474491634286592 |
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| author | Marine Lemesle Marine Geoffroy Fabien Alpy Catherine-Laure Tomasetto Sandra Kuntz Isabelle Grillier-Vuissoz |
| author_facet | Marine Lemesle Marine Geoffroy Fabien Alpy Catherine-Laure Tomasetto Sandra Kuntz Isabelle Grillier-Vuissoz |
| author_sort | Marine Lemesle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:31:49Z |
| format | Article |
| id | doaj.art-29fd7a9390534d70aebd518240998e2e |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:31:49Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-29fd7a9390534d70aebd518240998e2e2023-11-23T23:20:44ZengMDPI AGCancers2072-66942022-10-011420502610.3390/cancers14205026CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to ChemotherapyMarine Lemesle0Marine Geoffroy1Fabien Alpy2Catherine-Laure Tomasetto3Sandra Kuntz4Isabelle Grillier-Vuissoz5CRAN, UMR 7039, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy, FranceCRAN, UMR 7039, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Centre National de la Recherche Scientifique (CNRS), UMR7104 and Université de Strasbourg, 67400 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Centre National de la Recherche Scientifique (CNRS), UMR7104 and Université de Strasbourg, 67400 Illkirch, FranceCRAN, UMR 7039, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy, FranceCRAN, UMR 7039, Université de Lorraine, 54506 Vandoeuvre-lès-Nancy, FranceTriple-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.https://www.mdpi.com/2072-6694/14/20/5026breast cancerTNBCchemotherapyCLDN1sensitivityapoptosis |
| spellingShingle | Marine Lemesle Marine Geoffroy Fabien Alpy Catherine-Laure Tomasetto Sandra Kuntz Isabelle Grillier-Vuissoz CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy Cancers breast cancer TNBC chemotherapy CLDN1 sensitivity apoptosis |
| title | CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy |
| title_full | CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy |
| title_fullStr | CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy |
| title_full_unstemmed | CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy |
| title_short | CLDN1 Sensitizes Triple-Negative Breast Cancer Cells to Chemotherapy |
| title_sort | cldn1 sensitizes triple negative breast cancer cells to chemotherapy |
| topic | breast cancer TNBC chemotherapy CLDN1 sensitivity apoptosis |
| url | https://www.mdpi.com/2072-6694/14/20/5026 |
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