C7 peptide inhibits hepatocellular carcinoma metastasis by targeting the HGF/c-Met signaling pathway.

Abstract

Hepatocellular carcinoma (HCC), characterized by a high rate of metastasis and recurrence after surgery, is caused by malignant proliferation of hepatocytes with epigenetic and/or genetic mutations. In particular, abnormal activation of the hepatocyte growth factor (HGF)-/c-mesenchymal-epithelial transition receptor (c-Met) axis is closely associated with HCC metastasis. Unfortunately, effective treatments or drugs that target the HGF/c-Met signaling pathway are still in the research pipeline. Here, a c-Met inhibitor named the C7 peptide, which can inhibit both HGF and c-Met, can significantly inhibit HGF-induced (but not EGF-induced) cell migration and suppress the phosphorylation of c-Met, Akt and Erk1/2. Moreover, the C7 peptide can also significantly suppress tumor metastasis in nude mice and the phosphorylation of c-Met. Together, our current findings, demonstrated that the C7 peptide can inhibit HGF-induced cancer cell migration and invasion through the inhibition of Akt and Erk1/2. Identification of a peptide that can block HGF/c-Met signaling provides new insight into the mechanism of HCC and future clinical treatments.

• Authors: Mingyuan Zhao, Yinhe Wang, Yan Liu, Wanchun Zhang, Yakun Liu, Xiaoming Yang, Yunxia Cao, Siying Wang
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 20 Issue 12 Pg. 1430-1442 ( 2019) ISSN: 1555-8576 [Electronic] United States
• PMID: 31441380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptide Fragments
• Peptide Library
• galanin (1-13)-spantide amide
• Substance P
• Hepatocyte Growth Factor
• Galanin
• Proto-Oncogene Proteins c-met

Topics

• Animals
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Galanin (pharmacology)
• Hepatocyte Growth Factor (metabolism)
• Humans
• Immunohistochemistry
• Liver Neoplasms (metabolism, pathology)
• Mice
• Peptide Fragments (pharmacology)
• Peptide Library
• Protein Binding
• Proto-Oncogene Proteins c-met (metabolism)
• Signal Transduction (drug effects)
• Substance P (analogs & derivatives, pharmacology)
• Xenograft Model Antitumor Assays