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.

中文翻译：

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Caveolin-1通过激活Wnt /β-catenin途径来增强HCC细胞的增殖和侵袭能力，从而上调Fut8的表达。

小窝蛋白1（Cav-1）是小窝蛋白的关键结构蛋白，通过参与肝细胞癌（HCC）中异常的蛋白糖基化而发挥致癌作用。但是，Cav-1调节糖基化和糖基转移酶表达的机制尚未完全确定。在这里，我们表明Cav-1促进了α-1,6-岩藻糖基转移酶（Fut8）的表达，这催化了GDP-岩藻糖向N-糖链核心结构的转移。在这项研究中，我们显示了具有低Fut8转录和蛋白质水平的小鼠HCC细胞系Hepa1-6也缺乏Cav-1表达，而小鼠HCC细胞系Hca-F具有强大的Fut8表达和高表达。 Cav-1的转录和蛋白质水平。随后，发现Hepa1-6中的Cav-1过表达激活Wnt /β-catenin信号传导，Fut8启动子区域可激活其转录。相比之下，Hca-F中Cav-1表达的敲低导致Wnt /β-catenin途径被显着抑制，从而减弱了Fut8的表达。我们进一步表明，Cav-1诱导的Fut8表达上调增强了体外小鼠HCC细胞的增殖和侵袭。我们目前的发现提供了分子证据，表明Cav-1在调节糖基转移酶表达中起重要作用，并且可能参与异常糖基化，介导HCC的增殖和侵袭。