Accumulating data suggest that metadherin (MTDH) may function as an oncogene. Our previous study showed that MTDH promotes hepatocellular carcinoma (HCC) metastasis via the epithelial-mesenchymal transition. In this study, we aim to further elucidate how MTDH promotes HCC metastasis. Using Co-immunoprecipitation (co-IP) and mass spectrometry, we found that MTDH can specifically bind to protein arginine methyltransferase 5 (PRMT5). Further functional assays revealed that PRMT5 overexpression promoted the proliferation and motility of HCC cells and that knockout of PRMT5 impeded the effect of MTDH. The immunohistochemistry assay/tissue microarray results showed that when MTDH was overexpressed in HCC cells, PRMT5 translocated from the nucleus to the cytoplasm, with the subsequent translocation of beta-catenin from the cytoplasm to the nucleus and upregulation of the WNT-beta-catenin signaling pathway. Further in vivo experiments suggested that PRMT5 and beta-catenin played a pivotal role in MTDH-mediated HCC metastasis. We therefore concluded that the MTDH-PRMT5 complex promotes HCC metastasis by regulating the WNT-beta-catenin signaling pathway.
[1]Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Dept Liver Surg & Transplantat, Liver Canc Inst,Zhongshan Hosp,Minist Educ, Shanghai, Peoples R China.
[2]Fudan Univ, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai, Peoples R China.
[3]Shanghai Jiao Tong Univ, Fac Basic Med, Sch Med, Shanghai 200025, Peoples R China.
[4]Fudan Univ, Zhong Shan Hosp, Dept Pathol, Shanghai 200032, Peoples R China.
[5]Shanghai Key Lab Organ Transplantat, Shanghai, Peoples R China.
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