Met degradation by SAIT301, a Met monoclonal antibody, reduces the invasion and migration of nasopharyngeal cancer cells via inhibition of EGR-1 expression

Abstract

Nasopharyngeal carcinoma (NPC) is a common malignant tumor with high invasive and metastatic potential. The hepatocyte growth factor (HGF)-Met signaling pathway has a critical role in mediating the invasive growth of many different types of cancer, including head and neck squamous cell carcinoma. HGF also stimulates NPC cell growth and invasion in the cell line model. In this study, we determined the inhibitory effect of Met, using a Met-targeting monoclonal antibody (SAIT301), on the invasive and growth potential of NPC cell lines. Met inhibition by SAIT301 resulted in highly significant inhibition of cell migration and invasion in both the HONE1 and HNE1 cell lines. In addition, we also found that co-treatment of SAIT301 and HGF decreased the anchorage-independent growth induced by HGF in HNE1 cell lines. After SAIT301 treatment, Met, together with its downstream signaling proteins, showed downregulation of p-Met and p-ERK, but not p-AKT, in both HONE1 and HNE1 cell lines. Interestingly, we found that HGF treatment of NPC cell lines induced early growth response protein (EGR-1) expression, which is involved in cell migration and invasion. In addition, co-treatment with SAIT301 and HGF inhibited the HGF-induced expression of EGR-1. Next, knockdown of EGR-1 using small-interfering RNA inhibited HGF-induced cell invasion in NPC cell lines, suggesting that the expression level of EGR-1 is important in HGF-induced cell invasion of NPC cells. Therefore, the results support that SAIT301 inhibited Met activation as well as the downstream EGR-1 expression and could have therapeutic potential in NPC. Taken together, we suggest that Met is an anticancer therapeutic target for NPC that warrants further investigation and clinical trials and SAIT301 may be a promising tool for NPC therapy.

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

“…The delay might occur whether p-FAK was mediated by p-Src or not. A previous study in the same cell lines using a Met antibody showed that the decrease in Slug started after 6 hours in HNE1 and 12 hours in HONE1, and this supports the idea of delayed effects of SAC in HONE cells [ 23 ]. We inferred that the migration and invasion of NPC cells was suppressed through the Met-FAK signaling pathway as illustrated in Fig.…”

Integrated analysis of microRNA regulatory network in nasopharyngeal carcinoma with deep sequencing

“…The mechanism of MET in many tumors has been well explored in various research [ 50 , 51 ]. In NPC, miR-34c had been clearly proved to target MET [ 37 ], and it was activated by hepatocyte growth factor (HGF), then modulated cellular proliferation, migration, invasion via inhibition of EGR-1 expression [ 52 , 53 ]. Furthermore, PHA-665752, MET inhibitor, could furthermore effectively affect the radiosensitivity of NPC and suppress NPC cells proliferation [ 54 ].…”

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

“…Egr-1 also directly affects cell proliferation in astrocytes, glioma cells, and mesangial cells (39)(40)(41). Additionally, it is closely related to EMT and cell invasion in nasopharyngeal cancer, human ovarian cancer, colon cancer, and thyroid cancer cells (20,42,43). Egr-1 serves different roles in different cancer cells.…”