SENP1 regulates hepatocyte growth factor-induced migration and epithelial-mesenchymal transition of hepatocellular carcinoma.

Abstract

The deregulation of HGF/c-Met signaling is implicated in epithelial-mesenchymal transition (EMT) and progress of hepatocellular carcinoma (HCC). However, the epigenetic mechanisms that HGF/c-Met regulates EMT and metastasis of HCC cells are less explored. In this study, we demonstrated that HCC cells express a high level of SUMO/sentrin-specific protease 1 (Senp1) which is induced by HGF/c-Met signals. Lentivirus-mediated small hairpin RNA (shRNA) transduction results in Senp1 silence in HCC cells. Senp1 silence reduces the HGF-induced proliferation and migration of HCC cells. Senp1 inhibition also induces HCC cell apoptosis and growth arrest. Furthermore, Senp1 knockdown inhibits epithelial-to-mesenchymal transition, with increase of E-cadherin and ZO-1 expression, decrease of fibronectin and N-cadherin expression. The EMT-related transcription factor Zeb1 was SUMO-modified and decreased in Senp1-silenced HCC cells. These results delineate that senp1 might play an important role in the regulation of HGF-induced invasion and migration of HCC cells.

• Authors: Wenwen Zhang, Huiyan Sun, Xuefeng Shi, Hua Wang, Chunping Cui, Fengjun Xiao, ChuTse Wu, Xiaozhong Guo, Lisheng Wang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 6 Pg. 7741-8 (Jun 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26695141 (Publication Type: Journal Article)

Chemical References

• Cell Adhesion Molecules
• HGF protein, human
• Neoplasm Proteins
• RNA, Small Interfering
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met
• Endopeptidases
• SENP1 protein, human
• Cysteine Endopeptidases

Topics

• Apoptosis
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Adhesion Molecules (biosynthesis, genetics)
• Cell Cycle Checkpoints
• Cell Division
• Cell Line, Tumor
• Cell Movement
• Cysteine Endopeptidases
• Endopeptidases (genetics, physiology)
• Epithelial-Mesenchymal Transition (genetics)
• Hepatocyte Growth Factor (physiology)
• Humans
• Liver Neoplasms (genetics, pathology)
• Neoplasm Proteins (antagonists & inhibitors, genetics, physiology)
• Protein Processing, Post-Translational
• Proto-Oncogene Proteins c-met (physiology)
• RNA Interference
• RNA, Small Interfering (genetics)
• Signal Transduction (genetics)
• Sumoylation
• Zinc Finger E-box-Binding Homeobox 1 (metabolism)