Journal
CARCINOGENESIS
Volume 41, Issue 2, Pages 130-138Publisher
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgz065
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Funding
- National Natural Science Funds of China [81402376, 81572296, 81572823, 81502028, 31601114]
- Shanghai Hospital Development Center [SHDC12015104]
- National Key Research and Development Program [2016YFC0902400]
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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.
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