دورية أكاديمية
AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2
| العنوان: | AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2 |
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| المؤلفون: | Chloé Philippe, Benoît Pinson, Jim Dompierre, Véronique Pantesco, Benoît Viollet, Bertrand Daignan-Fornier, Michel Moenner |
| المصدر: | Neoplasia: An International Journal for Oncology Research, Vol 20, Iss 6, Pp 555-562 (2018) |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz. This transcriptional signature, together with the observation of increased levels in phosphorylation of Lats1 and Yap1 proteins, suggested that the Hippo signaling pathway was activated by AICAR. This effect was observed in both fibroblasts and epithelial cells. Knockdown of Lats1/2 prevented the cytoplasmic delocalization of Yap1/Taz proteins in response to AICAR and conferred a higher resistance to the drug. These results indicate that activation of the most downstream steps of the Hippo cascade participates to the antiproliferative effects of AICAR. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1476-5586 1522-8002 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S1476558618300642; https://doaj.org/toc/1476-5586; https://doaj.org/toc/1522-8002 |
| DOI: | 10.1016/j.neo.2018.03.006 |
| URL الوصول: | https://doaj.org/article/f8b13ada0770436c8378f60106b2ad78 |
| رقم الأكسشن: | edsdoj.f8b13ada0770436c8378f60106b2ad78 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 14765586 15228002 |
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| DOI: | 10.1016/j.neo.2018.03.006 |