MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas
While the transmembrane glycoprotein mucin 1 (MUC1) is clustered at the apical borders of normal epithelial cells, with transformation and loss of polarity, MUC1 is found at high levels in the cytosol and is uniformly distributed over the entire surface of carcinoma cells, where it can promote tumor...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/2/391 |
| _version_ | 1797344403875954688 |
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| author | Emma Bourdon Thomas Swierczewski Marine Goujon Nihad Boukrout Sandy Fellah Cynthia Van der Hauwaert Romain Larrue Bruno Lefebvre Isabelle Van Seuningen Christelle Cauffiez Nicolas Pottier Michaël Perrais |
| author_facet | Emma Bourdon Thomas Swierczewski Marine Goujon Nihad Boukrout Sandy Fellah Cynthia Van der Hauwaert Romain Larrue Bruno Lefebvre Isabelle Van Seuningen Christelle Cauffiez Nicolas Pottier Michaël Perrais |
| author_sort | Emma Bourdon |
| collection | DOAJ |
| description | While the transmembrane glycoprotein mucin 1 (MUC1) is clustered at the apical borders of normal epithelial cells, with transformation and loss of polarity, MUC1 is found at high levels in the cytosol and is uniformly distributed over the entire surface of carcinoma cells, where it can promote tumor progression and adversely affects the response to therapy. Clear cell renal cell carcinoma (ccRCC), the main histotype of kidney cancer, is typically highly resistant to conventional and targeted therapies for reasons that remain largely unknown. In this context, we investigated whether MUC1 also plays a pivotal role in the cellular and molecular events driving ccRCC progression and chemoresistance. We showed, using loss- and gain-of-function approaches in ccRCC-derived cell lines, that MUC1 not only influences tumor progression but also induces a multi-drug-resistant profile reminiscent of the activation of ABC drug efflux transporters. Overall, our results suggest that targeting MUC1 may represent a novel therapeutic approach to limit ccRCC progression and improve drug sensitivity. |
| first_indexed | 2024-03-08T11:01:54Z |
| format | Article |
| id | doaj.art-2df7c28be4df47e99636c080f0ba21aa |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T11:01:54Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2df7c28be4df47e99636c080f0ba21aa2024-01-26T15:37:25ZengMDPI AGCancers2072-66942024-01-0116239110.3390/cancers16020391MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal CarcinomasEmma Bourdon0Thomas Swierczewski1Marine Goujon2Nihad Boukrout3Sandy Fellah4Cynthia Van der Hauwaert5Romain Larrue6Bruno Lefebvre7Isabelle Van Seuningen8Christelle Cauffiez9Nicolas Pottier10Michaël Perrais11Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, UMR-S1172, Neuroscience & Cognition, Alzheimer & Tauopathies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277–CANTHER–Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, FranceWhile the transmembrane glycoprotein mucin 1 (MUC1) is clustered at the apical borders of normal epithelial cells, with transformation and loss of polarity, MUC1 is found at high levels in the cytosol and is uniformly distributed over the entire surface of carcinoma cells, where it can promote tumor progression and adversely affects the response to therapy. Clear cell renal cell carcinoma (ccRCC), the main histotype of kidney cancer, is typically highly resistant to conventional and targeted therapies for reasons that remain largely unknown. In this context, we investigated whether MUC1 also plays a pivotal role in the cellular and molecular events driving ccRCC progression and chemoresistance. We showed, using loss- and gain-of-function approaches in ccRCC-derived cell lines, that MUC1 not only influences tumor progression but also induces a multi-drug-resistant profile reminiscent of the activation of ABC drug efflux transporters. Overall, our results suggest that targeting MUC1 may represent a novel therapeutic approach to limit ccRCC progression and improve drug sensitivity.https://www.mdpi.com/2072-6694/16/2/391MUC1kidney cancerchemoresistance |
| spellingShingle | Emma Bourdon Thomas Swierczewski Marine Goujon Nihad Boukrout Sandy Fellah Cynthia Van der Hauwaert Romain Larrue Bruno Lefebvre Isabelle Van Seuningen Christelle Cauffiez Nicolas Pottier Michaël Perrais MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas Cancers MUC1 kidney cancer chemoresistance |
| title | MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas |
| title_full | MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas |
| title_fullStr | MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas |
| title_full_unstemmed | MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas |
| title_short | MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas |
| title_sort | muc1 drives the progression and chemoresistance of clear cell renal carcinomas |
| topic | MUC1 kidney cancer chemoresistance |
| url | https://www.mdpi.com/2072-6694/16/2/391 |
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