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

  • Jian-ang Li
  • Tiantao Kuang
  • Ning Pu
  • Yuan Fang
  • Xu Han
  • Lei Zhang
  • Xuefeng Xu
  • Wenchuan Wu
  • Dansong Wang
  • Wenhui Lou
  • Yefei RongEmail author
Original Article
  • 93 Downloads

Abstract

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.

Keywords

Pancreatic cancer Tumorigenicity Ubiquitination TRAF6 MST1 Hippo–YAP NF-κB 

Notes

Acknowledgements

This work was sponsored by the National Natural Science Foundation of China (Grant No. 81401923) and the Program of Shanghai Subject Chief Scientist (Grant No. 17XD1401200).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pancreatic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.The Research Institution of General Surgery, Zhongshan HospitalFudan UniversityShanghaiChina

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