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

Authors
Lee, BS  | Kang, S  | Kim, KA | Song, YJ | Cheong, KH | Cha, HY | Kim, CH
Citation
Cell death & disease, 5. : e1159-e1159, 2014
Journal Title
Cell death & disease
ISSN
2041-4889
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.
MeSH

DOI
10.1038/cddis.2014.119
PMID
24722284
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Ajou Authors
강, 성운  |  김, 철호  |  이, 복순
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