Dosage-dependent regulation of VAV2 expression by steroidogenic factor-1 drives adrenocortical carcinoma cell invasion
| العنوان: | Dosage-dependent regulation of VAV2 expression by steroidogenic factor-1 drives adrenocortical carcinoma cell invasion |
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| المؤلفون: | Silviu Sbiera, Jérôme Bertherat, Maddy Parsons, Bruno Ragazzon, Estelle Robidel, Martin Fassnacht, Iuliu Sbiera, Aurélie Morin, Carmen Ruggiero, Enzo Lalli, Judith Favier, Mabrouka Doghman-Bouguerra |
| المصدر: | Science Signaling. 10 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Regulation of gene expression, Steroidogenic factor 1, VAV2, Cell Biology, Biology, medicine.disease, behavioral disciplines and activities, Biochemistry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Cell culture, 030220 oncology & carcinogenesis, Cancer research, medicine, Adrenocortical carcinoma, Guanine nucleotide exchange factor, Molecular Biology, Gene, Transcription factor, psychological phenomena and processes |
| الوصف: | Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis. Genomic studies have enabled progress in our understanding of the molecular bases of ACC, but factors that influence its prognosis are lacking. Amplification of the gene encoding the transcription factor steroidogenic factor-1 (SF-1; also known as NR5A1) is one of the genetic alterations common in ACC. We identified a transcriptional regulatory mechanism involving increased abundance of VAV2, a guanine nucleotide exchange factor for small GTPases that control the cytoskeleton, driven by increased expression of the gene encoding SF-1 in ACC. Manipulating SF-1 and VAV2 abundance in cultured ACC cells revealed that VAV2 was a critical factor for SF-1-induced cytoskeletal remodeling and invasion in culture (Matrigel) and in vivo (chicken chorioallantoic membrane) models. Analysis of ACC patient cohorts indicated that greater VAV2 abundance robustly correlated with poor prognosis in ACC patients. Because VAV2 is a druggable target, our findings suggest that blocking VAV2 may be a new therapeutic approach to inhibit metastatic progression in ACC patients. |
| تدمد: | 1937-9145 1945-0877 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::e060c51b8e09a98aee766b0099827967Test https://doi.org/10.1126/scisignal.aal2464Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........e060c51b8e09a98aee766b0099827967 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19379145 19450877 |
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