Versican V1 Promotes Proliferation And Metastasis Of Hepatocellular Carcinoma Through The Activation Of EGFR-PI3K-AKT Pathway

Versican has been reported to participate in carcinogenesis in several malignant tumors.However,the accurate role of Versican in hepatocellular carcinoma(HCC)remains an enigma.Our current study revealed that VersicanV1,a predominant isoform of Versican in liver,is significantly upregulated in HCC tissues and correlates with poor prognosis.Experiments showed that knockdown of VersicanV1 in HCC cells attenuate cancer cells malignancy both in vitro and in vivo.Further studies identify the positive role of VersicanV1 in aerobic glycolysis.Mechanistic investigation discovered the activation of EGFR-PI3K-AKT pathway in HCC cells expressing high VersicanV1.Moreover,EGF-like motif is indispensable for VersicanV1 to promote Warburg effect of HCC cells and subsequently,proliferation,invasion and metastasis ability via activation of EGFR-PI3K-AKT axis.Taken together,our research highlights a novel role of VersicanV1 in the progressilon of HCC,suggesting that Versican V1 is an indicator for prognosis and a potential therapeutic target of HCC.