Hypoxia frequently occurs in solid tumors, hepatocellular carcinoma included. Hypoxia-inducible factors (HIFs) upregulated in hypoxia can induce various downstream target genes to resist hypoxia stress, resulting in tumor growth, angiogenesis and metastasis in vivo. Therefore, hypoxia associated genes are usually cancer progression associated genes and can be potential therapy targets for cancer therapy. In our present work, we find that the hypoxia-inducible transcriptional factor, HIF1α, can directly upregulate the expression of the gene Ctnnd2, which codes the protein δ-Catenin. Then, δ-Catenin can stabilize β-Catenin by disrupting the destruction complex, which leads to the activation of Wnt signaling. As a result, δ-Catenin can promote the proliferation and migration of HCC cells in vitro, further enhance mice HCC tumorigenesis in vivo. In summary, our work reveals that δ-Catenin is a direct downstream target gene of HIF1α. It can activate Wnt signaling via β-Catenin stabilization. δ-Catenin can enhance HCC progression.
Keywords: HIF1α; Hepatocellular carcinoma; Hypoxia; Wnt/β-Catenin; δ-Catenin.
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