دورية أكاديمية
ARID1A‐deficient cells require HDAC6 for progression of endometrial carcinoma
| العنوان: | ARID1A‐deficient cells require HDAC6 for progression of endometrial carcinoma |
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| المؤلفون: | Cristina Megino‐Luque, Pol Sisó, Natalia Mota‐Martorell, Raúl Navaridas, Inés de laRosa, Izaskun Urdanibia, Manel Albertí‐Valls, Maria Santacana, Miquel Pinyol, Núria Bonifaci, Anna Macià, David Llobet‐Navas, Sònia Gatius, Xavier Matias‐Guiu, Núria Eritja |
| المصدر: | Molecular Oncology, Vol 16, Iss 11, Pp 2235-2259 (2022) |
| بيانات النشر: | Wiley |
| سنة النشر: | 2022 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | ACY1215, ARID1A, endometrial cancer, HDAC6, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | AT‐rich interactive domain‐containing protein 1A (ARID1A) loss‐of‐function mutation accompanied by a loss of ARID1A protein expression is frequently observed in endometrial carcinomas. However, the molecular mechanisms linking these genetic changes to the altered pathways regulating tumour initiation, maintenance and/or progression remain poorly understood. Thus, the main aim of this study was to analyse the role of ARID1A loss of function in endometrial tumorigenesis. Here, using different endometrial in vitro and in vivo models, such as tumoral cell lines, 3D primary cultures and metastatic or genetically modified mouse models, we show that altered expression of ARID1A is not enough to initiate endometrial tumorigenesis. However, in an established endometrial cancer context, ARID1A loss of function accelerates tumoral progression and metastasis through the disruption of the G2/M cell cycle checkpoint and ATM/ATR‐mediated DNA damage checkpoints, increases epithelial cell proliferation rates and induces epithelial mesenchymal transition through the activation of histone deacetylase 6 (HDAC6). Next, we demonstrated that the inhibition of HDAC6 function, using the HDAC6‐specific inhibitor ACY1215 or by transfection with HDAC6 short hairpin RNA (shRNA), can reverse the migratory and invasive phenotype of ARID1A‐knockdown cells. Further, we also show that inhibition of HDAC6 activity causes an apoptotic vulnerability to etoposide treatments in ARID1A‐deficient cells. In summary, the findings exposed in this work indicate that the inhibition of HDAC6 activity is a potential therapeutic strategy for patients suffering from ARID1A‐mutant endometrial cancer diagnosed in advanced stages. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| العلاقة: | https://doi.org/10.1002/1878-0261.13193Test; https://doaj.org/toc/1574-7891Test; https://doaj.org/toc/1878-0261Test; https://doaj.org/article/88829f0c96d5428fb487eeec1a5e9881Test |
| DOI: | 10.1002/1878-0261.13193 |
| الإتاحة: | https://doi.org/10.1002/1878-0261.13193Test https://doaj.org/article/88829f0c96d5428fb487eeec1a5e9881Test |
| رقم الانضمام: | edsbas.D5D1BCE |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13193 |