Previous studies have revealed that CUL4B is overexpressed in various types of cancer and that its overexpression is related to the progression and metastasis of tumors. However, the biological functions of CUL4B in the progression of head and neck squamous cell carcinoma (HNSCC) are still not well understood. In the current study, we aimed to determine the changes in biological functions and molecular events that are related to CUL4B overexpression. Interestingly, our results showed that CUL4B is upregulated in HNSCC and that its upregulation is associated with poor survival and worse histological grade. Overexpression of CUL4B promoted cancer cell growth, invasion, and migration, as well as epithelial-mesenchymal transition, whereas the loss of CUL4B abrogated these malignant phenotypes. Moreover, our mechanistic investigations suggest that the Wnt/β-catenin signaling pathway was activated by CUL4B overexpression. Treatment with a Wnt/β-catenin inhibitor decreased CUL4B-induced migration and invasion, establishing a key role of Wnt/β-catenin signaling in mediating the effects of CUL4B expression. Together, these results demonstrate a key contribution of CUL4B overexpression in the malignant behavior of HNSCC cells, at least in part through the stimulation of angiogenesis and the activation of the Wnt/β-catenin signaling pathway.
Keywords: CUL4B; HNSCC; Wnt/β-catenin signaling; angiogenesis; metastasis.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.