SRPX2, an independent prognostic marker, promotes cell migration and invasion in hepatocellular carcinoma.
Sushi repeat-containing protein X-linked 2 (SRPX2), a novel chondroitin sulfate proteoglycan, is overexpressed in human cancer. Recent studies have reported that SRPX2 overexpression is observed in gastrointestinal cancer, and promotes migration and invasion of cancer cells. While, the clinical significance and biological function of SRPX2 remain rarely known in hepatocellular carcinoma (HCC). Here, we found that the levels of SRPX2 in HCC tissues were notably overexpressed compared to non-cancerous specimens. Accordingly, the levels of SRPX2 were obviously up-regulated in HCC cells compared with LO2 cells. The positive expression of SRPX2 was prominently correlated with venous infiltration and advanced TNM tumor stage. Furthermore, SRPX2 expression acted as an independent prognostic marker for HCC patients. SRPX2 knockdown prominently inhibited the invasion and migration of HCCLM3 cells, while SRPX2 restoration enhanced these cellular biological behaviors of Hep3B cells in vitro. Moreover, SRPX2 knockdown suppressed pulmonary metastasis of HCCLM3 cells in nude mice. Mechanically, SRPX2 knockdown reduced the levels of phosphorylated focal adhesion kinase (p-FAK), p-AKT, matrix metallopeptidase 2 (MMP2) and MMP9 in HCCLM3 cells. In turn, SRPX2 overexpression promoted the activation of FAK/AKT pathway and increased MMP2/9 expression in Hep3B cells. Thus, SRPX2 contributes to migration and invasion of HCC cells probably by targeting FAK/AKT pathway-mediated MMP2/9 expression. SRPX2 potentially acts as an independent prognostic predictor and a drug-target for HCC patients.
['Lin|Xiaobo|X|', 'Chang|Weiping|W|', 'Wang|Yuan|Y|', 'Tian|Ming|M|', 'Yu|Zhaoxiang|Z|']
D000818:Animals D014408:Biomarkers, Tumor D006528:Carcinoma, Hepatocellular D045744:Cell Line, Tumor D002465:Cell Movement D051416:Focal Adhesion Protein-Tyrosine Kinases D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D006801:Humans D008113:Liver Neoplasms D008175:Lung Neoplasms D008565:Membrane Proteins D008807:Mice, Inbred BALB C D008819:Mice, Nude D015999:Multivariate Analysis D009361:Neoplasm Invasiveness D009363:Neoplasm Proteins D009419:Nerve Tissue Proteins D011379:Prognosis D051057:Proto-Oncogene Proteins c-akt D012044:Regression Analysis D015854:Up-Regulation
SRPX2 HCC FAK/AKT pathway MMP2/9 Tumor metastasis