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.

Five gene signatures were identified in the prediction of overall survival in resectable pancreatic cancer

“…Methyltransferase (MET) is a proto-oncogene encoding the receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF) [42], which triggers cell migration, proliferation, and angiogenesis. Aberrant MET expression is commonly expressed in various malignancies [43][44][45][46][47]. The protein coded by CHFR (Checkpoint with fork head and ring finger domains) serves as a checkpoint that might play diverse roles at different phases of the cell cycle [48,49].…”

Down-regulation of the tumor suppressor miR-34a contributes to head and neck cancer by up-regulating the MET oncogene and modulating tumor immune evasion

“…MET is a receptor tyrosine kinase [ 30 ], deregulated in many types of human malignancies including breast cancer, lung cancer, bladder cancer, hepatocellular carcinoma, and melanoma [ 31 , 32 ]. Although abnormal activation of MET in some cancers, such as hepatocellular carcinoma, is known to be correlated with poor prognosis [ 33 ], the role of the miR-34a-MET axis in HNSCC has not been investigated. Additionally, the role of miR-34a in the tumor microenvironment in HNSCC is also yet to be elucidated.…”

Nanomedicine in Hepatocellular Carcinoma: A New Frontier in Targeted Cancer Treatment

“…Peptides, by virtue of their small size, possess a number of unique features defining them as promising therapeutic agents that include effective tissue penetration as well as negligence to the host immune system leading to lesser or no off-target effects and adverse effects [290]. Some of the studied peptides in HCC include SP94 [291][292][293], Tv1 [294][295][296][297], FFW [298,299], iRGD [83,91,300], GG-8-6 [301], BR2 [302,303], β3 [304], GW-H1 [305,306], bovicin HC5 [307], R-Tf-D-LP4 [308], C7 [309], HCC79 [289,310], GPC3 peptide [311][312][313] and cecropinXJ [290,314]. Peptides are also being investigated in HCC vaccine development, targeting specifically overexpressed targets such as GPC3 [315].…”