Open AccessTumor necrosis factor receptor‐associated factor 6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation
Author(s) -
Shi Jianbo,
Liu Zengying,
Xu Qin
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14012
Subject(s) - cancer research , carcinogenesis , ubiquitin ligase , protein kinase b , cancer , tumor necrosis factor alpha , phosphorylation , growth factor receptor , ubiquitin , biology , medicine , microbiology and biotechnology , genetics , gene
Tumor necrosis factor receptor‐associated factor 6 (TRAF6) has been found to be involved in carcinogenesis in multiple cancers. However, the precise role of TRAF6 in cancer has not been extensively investigated and remains largely unknown. In this study, we aimed to investigate the biological function of TRAF6 and its underlying molecular mechanisms in cancer. A positive correlation between poor tumor differentiation and TRAF6 expression status was observed in both oral cancer and breast cancer. Overexpression of TRAF6 promoted proliferation, migration, and G 0 /G 1 to S phase transition in tumor cells. Tumor necrosis factor receptor‐associated factor 6‐mediated AKT ubiquitination and subsequent phosphorylation played an essential role in the control of tumor cell malignant behavior. In vivo treatment with TRAF6, but not the E3 ligase deficient TRAF6 mutant, facilitated tumor growth. Our findings indicate that TRAF6 contributes to malignant behavior of human cancers through promoting AKT ubiquitination and phosphorylation. Therefore, TRAF6 could serve as a therapeutic target in cancers.