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10.1038/cdd.2016.143

http://scihub22266oqcxt.onion/10.1038/cdd.2016.143
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C5457685!5457685!28009353
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suck abstract from ncbi


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pmid28009353      Cell+Death+Differ 2017 ; 24 (3): 469-80
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  • Pellino-1 promotes lung carcinogenesis via the stabilization of Slug and Snail through K63-mediated polyubiquitination #MMPMID28009353
  • Jeon YK; Kim CK; Hwang KR; Park HY; Koh J; Chung DH; Lee CW; Ha GH
  • Cell Death Differ 2017[Mar]; 24 (3): 469-80 PMID28009353show ga
  • Pellino-1 is an E3 ubiquitin ligase acting as a critical mediator for a variety of immune receptor signaling pathways, including Toll-like receptors, interleukin-1 receptor and T-cell receptors. We recently showed that the Pellino-1-transgenic (Tg) mice developed multiple tumors with different subtypes in hematolymphoid and solid organs. However, the molecular mechanism underlying the oncogenic role of Pellino-1 in solid tumors remains unknown. Pellino-1-Tg mice developed adenocarcinoma in the lungs, and Pellino-1 expression was higher in human lung adenocarcinoma cell lines compared with non-neoplastic bronchial epithelial cell lines. Pellino-1 overexpression increased the cell proliferation, survival, colony formation, invasion and migration of lung adenocarcinoma cells, whereas Pellino-1 knock-down showed the opposite effect. Pellino-1 overexpression activated PI3K/Akt and ERK signaling pathways and elicited an epithelial?mesenchymal transition (EMT) phenotype of lung adenocarcinoma cells. Pellino-1-mediated EMT was demonstrated through morphology, the upregulation of Vimentin, Slug and Snail expression and the downregulation of E-cadherin and ?-catenin expression. Notably, Pellino-1 had a direct effect on the overexpression of Snail and Slug through Lys63-mediated polyubiquitination and the subsequent stabilization of these proteins. Pellino-1 expression level was significantly correlated with Snail and Slug expression in human lung adenocarcinoma tissues, and lung tumors from Pellino-1-Tg mice showed Snail and Slug overexpression. The Pellino-1-mediated increase in the migration of lung adenocarcinoma cells was mediated by Snail and Slug expression. Taken together, these results show that Pellino-1 contributes to lung tumorigenesis by inducing overexpression of Snail and Slug and promoting EMT. Pellino-1 might be a potential therapeutic target for lung cancer.
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