SIAH1/CTR9 axis promotes the epithelial-mesenchymal transition of hepatocellular carcinoma.
Zhiyi LiuPengchao LuoKuan CaoQinghe HuBin HuLicheng CuiXiaotian WangHengliang ShiBin ZhangRenhao WangPublished in: Carcinogenesis (2023)
SIAH1 has been reported to participate in several human cancers, including HCC. However, the effect of SIAH1 on the EMT has not been reported in HCC cells. Here, we discovered the inhibitory effect of SIAH1 on HCC cell migration and invasion, which was related with regulating EMT. Molecularly, a yeast two-hybrid experiment indicated that CTR9 was a potential interacting protein of SIAH1, which was further verified by co-immunoprecipitation (co-IP) assays. Furthermore, SIAH1 inhibited the EMT of HCC cells through negatively regulating CTR9. Importantly, CTR9 was ubiquitinated and degraded by SIAH1 via the proteasome pathway in HCC cells. Additionally, it was showed that SIAH1 mainly mediated the K48-linked polyubiquitination on CTR9. Finally, the protein level of CTR9 was found to be inversely correlated with SIAH1 in human HCC tissues. Summed up all together, these findings reveal that SIAH1/CTR9 axis promotes the EMT of HCC cells and is a promising therapeutic target for HCC therapy.
Keyphrases
- epithelial mesenchymal transition
- induced apoptosis
- cell cycle arrest
- endothelial cells
- signaling pathway
- oxidative stress
- transforming growth factor
- cell death
- climate change
- human health
- mesenchymal stem cells
- binding protein
- small molecule
- bone marrow
- saccharomyces cerevisiae
- pluripotent stem cells
- genome wide
- replacement therapy