TRAF1 is critical for regulating the BRAF/MEK/ERK pathway in non–small cell lung carcinogenesis

Qiushi Wang, Ge Gao, Tianshun Zhang, Ke Yao, Hanyong Chen, Mi Hee Park, Hiroyuki Yamamoto, Keke Wang, Weiya Ma, Margarita Malakhova, Ann M. Bode, Zigang Dong

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Tumor necrosis factor receptor (TNFR)–associated factor 1 (TRAF1) is a unique TRAF protein that can interact directly or indirectly with multiple TNFR family members, regulatory proteins, kinases, and adaptors that contribute to its diverse functions in specific tissues. However, the role of TRAF1 in non–small cell lung cancer (NSCLC) remains unknown. In this study, we report that TRAF1 is overexpressed in human lung cancer cells and tissues. TRAF1 expression level inversely correlated with patient survival probability. Loss of TRAF1 decelerated tumor invasion in a urethane-induced lung carcinogenesis mouse model. Furthermore, TRAF1 expression affected TRAF2-mediated BRAF Lys48–linked ubiquitination, which was followed by the inhibition of growth and differentiation, and the induction of death in lung cancer cells. Overall, our work suggests that TRAF1 plays a novel role in the regulation of the BRAF/MEK/ERK signaling pathway in NSCLC and offers a candidate molecular target for lung cancer prevention and therapy. Significance: These findings identify TRAF1 as a new therapeutic target for NSCLC.

Original languageEnglish (US)
Pages (from-to)3982-3994
Number of pages13
JournalCancer Research
Issue number14
StatePublished - Jul 15 2018

Bibliographical note

Funding Information:
The authors thank Todd Schuster for supporting experiments, Tara Adams for supporting animal experiments, and Dr. Tia Rai for assistance in submitting our article (The Hormel Institute, University of Minnesota). This work was supported by the Hormel Foundation and NIH grants CA166011, CA187027, and CA196639 (Z. Dong).

Publisher Copyright:
©2018 American Association for Cancer Research.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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