Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR)
Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler B...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/6/1518 |
| _version_ | 1797446920889696256 |
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| author | Raúl Muñoz Velasco Paula Jiménez Sánchez Ana García García Raquel Blanco Martinez-Illescas Ángela Pastor Senovilla Marian Lozano Yagüe Alfonsina Trento Rosa María García-Martin Diego Navarro Bruno Sainz José Luis Rodríguez Peralto Víctor Javier Sánchez-Arévalo Lobo |
| author_facet | Raúl Muñoz Velasco Paula Jiménez Sánchez Ana García García Raquel Blanco Martinez-Illescas Ángela Pastor Senovilla Marian Lozano Yagüe Alfonsina Trento Rosa María García-Martin Diego Navarro Bruno Sainz José Luis Rodríguez Peralto Víctor Javier Sánchez-Arévalo Lobo |
| author_sort | Raúl Muñoz Velasco |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine. |
| first_indexed | 2024-03-09T13:47:32Z |
| format | Article |
| id | doaj.art-cc5b85914d984f2aa44ac46dc3ba37e9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:47:32Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cc5b85914d984f2aa44ac46dc3ba37e92023-11-30T20:56:32ZengMDPI AGCancers2072-66942022-03-01146151810.3390/cancers14061518Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR)Raúl Muñoz Velasco0Paula Jiménez Sánchez1Ana García García2Raquel Blanco Martinez-Illescas3Ángela Pastor Senovilla4Marian Lozano Yagüe5Alfonsina Trento6Rosa María García-Martin7Diego Navarro8Bruno Sainz9José Luis Rodríguez Peralto10Víctor Javier Sánchez-Arévalo Lobo11Molecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainMolecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainMolecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainMolecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainMolecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainMolecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainPathology Department, Hospital 12 de Octubre, Av. Córdoba, s/n, 28041 Madrid, SpainPathology Department, Hospital 12 de Octubre, Av. Córdoba, s/n, 28041 Madrid, SpainDepartment of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), CSIC-UAM, 28029 Madrid, SpainDepartment of Cancer Biology, Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), CSIC-UAM, 28029 Madrid, SpainPathology Department, Hospital 12 de Octubre, Av. Córdoba, s/n, 28041 Madrid, SpainMolecular Oncology Group, Biosanitary Research Institute, Faculty of Experimental Sciences, Francisco de Vitoria University (UFV), 28223 Madrid, SpainPancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.https://www.mdpi.com/2072-6694/14/6/1518BPTFpancreatic cancerABC-transportersmultidrug resistancegemcitabine |
| spellingShingle | Raúl Muñoz Velasco Paula Jiménez Sánchez Ana García García Raquel Blanco Martinez-Illescas Ángela Pastor Senovilla Marian Lozano Yagüe Alfonsina Trento Rosa María García-Martin Diego Navarro Bruno Sainz José Luis Rodríguez Peralto Víctor Javier Sánchez-Arévalo Lobo Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR) Cancers BPTF pancreatic cancer ABC-transporters multidrug resistance gemcitabine |
| title | Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR) |
| title_full | Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR) |
| title_fullStr | Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR) |
| title_full_unstemmed | Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR) |
| title_short | Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR) |
| title_sort | targeting bptf sensitizes pancreatic ductal adenocarcinoma to chemotherapy by repressing abc transporters and impairing multidrug resistance mdr |
| topic | BPTF pancreatic cancer ABC-transporters multidrug resistance gemcitabine |
| url | https://www.mdpi.com/2072-6694/14/6/1518 |
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