| Autor: |
Tingting Huang, Esteban Rozen, Qiong Wu, Xiao-Ou Zhang, Gang Wang, Lei Zhang, Lei Huang, Jason M. Shohet, Xiaomei Sun, Benjamin Sallis, Kim Wigglesworth, Daniel Moon, Odette Verdejo-Torres, Mary M. Lee |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.08.12.246660 |
| Popis: |
Protein arginine methyltransferase 5 (PRMT5) regulates a wide range of physiological processes, including cancer cell proliferation and metastasis, by generating symmetric di-methyl-arginine marks on histones and non-histone proteins. Here, we report that PRMT5 directly regulates epidermal growth factor receptor (EGFR) transcription to control EGF stimulated EGFR signaling. Furthermore, PRMT5 modulates protein kinase B (AKT) activation by methylation of AKT1 Arg 15, which is required for its subsequent phosphorylation at AKT1 Thr 308 and Ser 473. The PRMT5/EGFR/AKT axis converges to regulate transcription factors ZEB1, SNAIL, and TWIST1 to promote the epithelial-mesenchymal transition (EMT), in the manner that EGFR and AKT1 compensate each other to support tumor cell invasion and metastasis. Inhibiting PRMT5 methyltransferase activity with a small molecule inhibitor attenuated primary tumor growth and prevented hepatic metastasis in aggressive in vivo tumor models. Collectively, our results support the use of PRMT5 based therapies for metastatic cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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