TAB3 upregulates Survivin expression to promote colorectal cancer invasion and metastasis by binding to the TAK1-TRAF6 complex

Oncotarget. 2017 Nov 18;8(63):106565-106576. doi: 10.18632/oncotarget.22497. eCollection 2017 Dec 5.

Abstract

Transforming growth factor-β-activated kinase 1 (TAK1)-binding protein 3 (TAB3) is involved in cancer proliferation and metastasis, but its role in colorectal cancer remains unclear. In this study, we demonstrated that TAB3 is upregulated in colorectal cancer tissues and that high TAB3 levels correlated with tumor metastasis and a poor prognosis in colorectal cancer. In addition, TAB3 knockdown decreased Survivin expression and suppressed colorectal cancer cell migration and invasion in vitro, and reduced liver metastasis in vivo. Importantly, we found that TAB3 regulated Survivin expression by activating the NF-κB pathway through the formation of the TAK1-TAB3-TRAF6 complex. These findings suggest TAB3 may be a useful prognostic biomarker in colorectal cancer and a target for treatment of metastatic colorectal cancer.

Keywords: NF-κB pathway; Survivin; TAB3; colorectal cancer; metastasis.