Academic Journal
ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to chemotherapy in lung cancer
| العنوان: | ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to chemotherapy in lung cancer |
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| المؤلفون: | Moreno Rodríguez, Thaidy, Monterde Martínez, Beatriz, González Silva, Laura, Betancor-Fernández, Isabel, Revilla Gómez, Carlos, Agraz Doblas, Antonio, Freire, Javier, Isidro, Pablo, Quevedo Palacio, Laura, Blanco Fernández, Rosa, Montes-Moreno, Santiago, Cereceda, Laura, Astudillo, Aurora, Casar Martínez, Berta, Crespo Baraja, Pedro, Morales Torres, Cristina, Scaffidi, Paola, Gómez-Román, Javier, Salido, Eduardo, Varela Egocheaga, Ignacio |
| المساهمون: | Universidad de Cantabria |
| المصدر: | Oncogene 2021 Apr;40(16):2923-2935 |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2021 |
| المجموعة: | Universidad de Cantabria: UCrea |
| مصطلحات موضوعية: | ARID2, Lung Cancer, Next-generation sequencing technologies, SWI/SNF |
| الوصف: | The survival rate in lung cancer remains stubbornly low and there is an urgent need for the identification of new therapeutic targets. In the last decade, several members of the SWI/SNF chromatin remodeling complexes have been described altered in different tumor types. Nevertheless, the precise mechanisms of their impact on cancer progression, as well as the application of this knowledge to cancer patient management are largely unknown. In this study, we performed targeted sequencing of a cohort of lung cancer patients on genes involved in chromatin structure. In addition, we studied at the protein level the expression of these genes in cancer samples and performed functional experiments to identify the molecular mechanisms linking alterations of chromatin remodeling genes and tumor development. Remarkably, we found that 20% of lung cancer patients show ARID2 protein loss, partially explained by the presence of ARID2 mutations. In addition, we showed that ARID2 deficiency provokes profound chromatin structural changes altering cell transcriptional programs, which bolsters the proliferative and metastatic potential of the cells both in vitro and in vivo. Moreover, we demonstrated that ARID2 deficiency impairs DNA repair, enhancing the sensitivity of the cells to DNA-damaging agents. Our findings support that ARID2 is a bona fide tumor suppressor gene in lung cancer that may be exploited therapeutically. ; Financial Support: I. V. is supported by SAF2012-31627 and SAF2016-76758-R grants from the Spanish Ministerio de Economía y Competitividad (MINECO), by a Fundación Ramón Areces grant and by ERC2014-StG637904 grant from the European Research Council. I. V has been awardee of the Programa Ramón y Cajal (MINECO, Spain). T. M has been awardee of the Ayudas para la contratación de investigadores predoctorales (MINECO, Spain). B. M is awardee of the Ayudas para la formación de profesorado universitario (FPU, Ministerio de Educación y Formación Profesional, Spain). PC laboratory is supported by grant SAF-2015-63638R ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0950-9232 1476-5594 |
| Relation: | https://www.doi.org/10.1038/s41388-021-01748-y; SAF2012-31627; SAF2016-76758-R; SAF-2015-63638R; SAF-2015-73364-JIN; http://hdl.handle.net/10902/23854 |
| DOI: | 10.1038/s41388-021-01748-y |
| الاتاحة: | http://hdl.handle.net/10902/23854 https://doi.org/10.1038/s41388-021-01748-y |
| Rights: | ©Macmillan Publishers Limited, part of Springer Nature ; openAccess |
| رقم الانضمام: | edsbas.A40490B |
| قاعدة البيانات: | BASE |
| تدمد: | 09509232 14765594 |
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| DOI: | 10.1038/s41388-021-01748-y |