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.
Highlights
Colorectal cancer (CRC) is one of the most common types of cancer and a leading cause of cancer-related deaths worldwide [1]
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
The results revealed that high TAB3 expression was significantly associated with lymphatic metastasis (P < 0.001), venous invasion (P = 0.036) and advanced TNM stage (P = 0.001), indicating that TAB3 overexpression is involved in CRC aggressiveness and metastasis (Table 1)
Summary
Colorectal cancer (CRC) is one of the most common types of cancer and a leading cause of cancer-related deaths worldwide [1]. Metastasis and recurrence are the major causes of death in CRC. A member of the inhibitor of apoptosis (IAP) protein family that inhibits caspases and blocks cell death, is highly expressed in most cancers and is associated with a poor clinical outcome [3, 4]. Prior studies demonstrated that knockdown of Survivin in glioma inhibited angiogenesis [7], Survivin overexpression enhanced human melanocyte and melanoma cell migration [8] and Survivin promoted tumor cell invasion in vitro and metastatic dissemination in an in vivo murine model of breast cancer [9]. In CRC, Survivin overexpression is an independent poor prognostic factor in patients, and knockdown of Survivin could significantly inhibit CRC invasion and metastasis [10].These studies suggest that Survivin may play an important role in tumor invasion and metastasis
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