Caveolin‐1 upregulates Fut8 expression by activating the Wnt/β‐catenin pathway to enhance HCC cell proliferative and invasive ability
Cheng Zhang, Qiong Wu, Huang Huang, Xixi Chen, Tianmiao Huang, Wenli Li, Jianing Zhang, Yubo Liu
Abstract
Caveolin-1 (Cav-1), a critical structural protein of caveolae, plays an oncogenic role by participating in abnormal protein glycosylation in hepatocellular carcinoma (HCC). However, the mechanism by which Cav-1 regulates glycosylation and glycosyltransferase expression has yet to be fully defined. Here, we show that Cav-1 promotes the expression of α-1,6-fucosyltransferase (Fut8), which catalyzes the transfer of GDP-fucose to the core structure of the N-sugar chain. In this study, we show that the mouse HCC cell line, Hepa1-6, which has low Fut8 transcriptional and protein levels, also lacks Cav-1 expression, whereas the mouse HCC cell line, Hca-F, has strong Fut8 expression and high transcriptional and protein levels of Cav-1. Subsequently, Cav-1 overexpression in Hepa1-6 was found to activate Wnt/β-catenin signaling, which leads to downstream binding of the T cell factor/lymphoid enhancer factor to the Fut8 promoter region for activation of its transcription. In contrast, knockdown of Cav-1 expression in Hca-F caused the Wnt/β-catenin pathway to be significantly inhibited, which attenuates the expression of Fut8. We further show that Cav-1-induced upregulation of Fut8 expression enhanced proliferation and invasion by mouse HCC cells in vitro. Our current findings provide molecular evidence that Cav-1 plays an important role in regulating glycosyltransferase expression and may participate in abnormal glycosylation, which mediates the proliferation and invasion of HCC.