Our research aims to identify the role of thrombospondin 4 (THBS4) in hepatocellular carcinoma (HCC). First, bioinformatic analysis was applied for detection the expression of THBS4 in HCC samples, and qRT-PCR and western blot were performed to explore the expression of THBS4 in HCC tissues and adjacent samples. Next, colony formation assay and cell viability assay were used to assess the function of THBS4 on HCC cells growth while transwell assay and scratch test were for metastasis. Meanwhile Xenograft tumor models were further conducted to verify the function of THBS4 in HCC. As for mechanism in deep, we investigated the influence of THBS4 on epithelial-mesenchymal transition (EMT) development and the interaction between THBS4 and integrin (ITG) family using multiple experiments, including western blot, immunofluorescence and immunoprecipitation (IP). As a result, our research discovered that the overexpression of THBS4 in both HCC patients' tissues and cell lines mediates HCC cells proliferation and metastasis in vitro and in vivo. In-depth, THBS4 regulated EMT progression and interacted with ITG family to modulate FAK/PI3K/AKT pathway. In conclusion, THBS4 as an oncogene interacts with integrinβ1 (ITGB1) to regulate HCC development via FAK/PI3K/AKT pathway.
Keywords: FAK/PI3K/AKT pathway; epithelial-mesenchymal transition; hepatocellular carcinoma development; integrinβ1; thrombospondin 4.
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