Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma
The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment....
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/3038 |
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| author | Mickaël Burgy Aude Jehl Ombline Conrad Sophie Foppolo Véronique Bruban Nelly Etienne-Selloum Alain C. Jung Murielle Masson Christine Macabre Sonia Ledrappier Hélène Burckel Carole Mura Georges Noël Christian Borel François Fasquelle Mihaela-Alina Onea Marie-Pierre Chenard Alicia Thiéry Monique Dontenwill Sophie Martin |
| author_facet | Mickaël Burgy Aude Jehl Ombline Conrad Sophie Foppolo Véronique Bruban Nelly Etienne-Selloum Alain C. Jung Murielle Masson Christine Macabre Sonia Ledrappier Hélène Burckel Carole Mura Georges Noël Christian Borel François Fasquelle Mihaela-Alina Onea Marie-Pierre Chenard Alicia Thiéry Monique Dontenwill Sophie Martin |
| author_sort | Mickaël Burgy |
| collection | DOAJ |
| description | The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC. |
| first_indexed | 2024-03-10T10:18:53Z |
| format | Article |
| id | doaj.art-cf6ec7c6c2d54937afdc4489ee108c8f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:18:53Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cf6ec7c6c2d54937afdc4489ee108c8f2023-11-22T00:39:19ZengMDPI AGCancers2072-66942021-06-011312303810.3390/cancers13123038Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell CarcinomaMickaël Burgy0Aude Jehl1Ombline Conrad2Sophie Foppolo3Véronique Bruban4Nelly Etienne-Selloum5Alain C. Jung6Murielle Masson7Christine Macabre8Sonia Ledrappier9Hélène Burckel10Carole Mura11Georges Noël12Christian Borel13François Fasquelle14Mihaela-Alina Onea15Marie-Pierre Chenard16Alicia Thiéry17Monique Dontenwill18Sophie Martin19Laboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC U1113, Université de Strasbourg, 67200 Strasbourg, FranceUMR7242 Biotechnologie et Signalisation Cellulaire, Ecole Supérieure de Biotechnologie de Strasbourg, 67412 Illkirch, FranceLaboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC U1113, Université de Strasbourg, 67200 Strasbourg, FranceLaboratory STREINTH (Stress Response and Innovative Therapies), Inserm IRFAC U1113, Université de Strasbourg, 67200 Strasbourg, FrancePaul Strauss Comprehensive Cancer Center, Radiobiology Laboratory, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg University, UNICANCER, 67000 Strasbourg, FrancePaul Strauss Comprehensive Cancer Center, Radiobiology Laboratory, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg University, UNICANCER, 67000 Strasbourg, FrancePaul Strauss Comprehensive Cancer Center, Radiobiology Laboratory, Institut de Cancérologie Strasbourg Europe (ICANS), Strasbourg University, UNICANCER, 67000 Strasbourg, FranceDepartment of Medical Oncology, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, FranceInstitut Pathology, University Hospital of Lausanne, 1011 Lausanne, SwitzerlandDepartment of Pathology, Strasbourg University Hospital, 67200 Strasbourg, FranceDepartment of Pathology, Strasbourg University Hospital, 67200 Strasbourg, FranceDepartment of Public Health, Institut de Cancérologie Strasbourg Europe, 67200 Strasbourg, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceLaboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, 67401 Illkirch, FranceThe EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.https://www.mdpi.com/2072-6694/13/12/3038head and neck cancerbiomarkersEGFR therapy |
| spellingShingle | Mickaël Burgy Aude Jehl Ombline Conrad Sophie Foppolo Véronique Bruban Nelly Etienne-Selloum Alain C. Jung Murielle Masson Christine Macabre Sonia Ledrappier Hélène Burckel Carole Mura Georges Noël Christian Borel François Fasquelle Mihaela-Alina Onea Marie-Pierre Chenard Alicia Thiéry Monique Dontenwill Sophie Martin Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma Cancers head and neck cancer biomarkers EGFR therapy |
| title | Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma |
| title_full | Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma |
| title_fullStr | Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma |
| title_full_unstemmed | Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma |
| title_short | Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma |
| title_sort | cav1 ereg yap axis in the treatment resistance of cav1 expressing head and neck squamous cell carcinoma |
| topic | head and neck cancer biomarkers EGFR therapy |
| url | https://www.mdpi.com/2072-6694/13/12/3038 |
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