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.

KEYWORDS:

• C7 peptide
• hepatocellular carcinoma (HCC)
• HGF/c-Met axis
• migration
• invasion

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Supplementary material

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Additional information

Funding

This work was supported by Chinese National “973” Science Foundation, Grant number: [2002CB513100] and National Natural Sciences Foundation of China, Grant number [81772988].