TRAF6 regulates YAP signaling by promoting the ubiquitination and degradation of MST1 in pancreatic cancer

Clinical and Experimental Medicine(2019)

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摘要
TNF receptor-associated factor 6 (TRAF6), a regulator of NF-κB signaling, has been reported to be associated with the oncogenesis of various tumors including pancreatic cancer, but the underlying mechanisms remain unknown. Here, we found that knocking down the expression of TRAF6 impaired YAP signaling. Moreover, TRAF6 promoted the migration and colony formation of pancreatic cancer cells through YAP. Then, we found that TRAF6 interacted with and promoted the ubiquitination and degradation of MST1, and the expression of TRAF6 and MST1 was negatively correlated in primary human pancreatic cancer samples. Our results reveal that TRAF6 regulates YAP signaling by promoting the ubiquitination and degradation of MST1 in pancreatic cancer, suggesting that TRAF6 could be a possible E3 ligase of MST1 and a potential therapeutic target.
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关键词
Pancreatic cancer, Tumorigenicity, Ubiquitination, TRAF6, MST1, Hippo–YAP, NF-κB
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