TY - JOUR
T1 - TRAF1 is critical for regulating the BRAF/MEK/ERK pathway in non–small cell lung carcinogenesis
AU - Wang, Qiushi
AU - Gao, Ge
AU - Zhang, Tianshun
AU - Yao, Ke
AU - Chen, Hanyong
AU - Park, Mi Hee
AU - Yamamoto, Hiroyuki
AU - Wang, Keke
AU - Ma, Weiya
AU - Malakhova, Margarita
AU - Bode, Ann M.
AU - Dong, Zigang
N1 - Publisher Copyright:
©2018 American Association for Cancer Research.
PY - 2018/7/15
Y1 - 2018/7/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-18-0429
DO - 10.1158/0008-5472.CAN-18-0429
M3 - Article
C2 - 29748372
AN - SCOPUS:85050697238
SN - 0008-5472
VL - 78
SP - 3982
EP - 3994
JO - Cancer Research
JF - Cancer Research
IS - 14
ER -