Silencing of c-Met by RNA interference inhibits the survival, proliferation, and invasion of nasopharyngeal carcinoma cells

Li, Yuncheng; Zhang, Sulin; Tang, Zehai; Chen, Jian; Kong, Weijia

doi:10.1007/s13277-011-0225-y

“…Similar to our results, Li et al 35 reported that knockdown of Met using siRNA inhibits the survival, proliferation and invasion of NPC cells. Zhou et al 24 demonstrated that HGF, which is involved in the invasive phenotype and motility of NPC cells, is mediated by JNK through upregulation of MMP-9.…”

Section: Discussionsupporting

confidence: 93%

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

Bs

¹

,

Kang

²

,

Ka

³

et al. 2014

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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.

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“…MET plays a critical role during embryogenesis and tissue repair and remodeling in adults [8]. Aberrant activation of MET has been detected in various cancers [9][10][11][12][13][14], including TC [15,16]. Nevertheless, its regulation in TC remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Regulation of MET-mediated proliferation of thyroid carcinoma cells by miR-449b

Chen

¹

,

Liu

²

,

Wang

³

2015

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Thyroid carcinoma (TC) is a lethal cancer worldwide, whereas its carcinogenesis is not fully understood. Although growing evidence has demonstrated that dysregulation of microRNAs (miRNAs) contributes to the development of various cancers, the role of miRNAs in the pathogenesis of TC is poorly characterized. Here, we analyzed the levels of miR-449b in TC tissues and detected significantly lower miR-449b levels in TC tissues. Moreover, the low miR-449b levels were associated with poor survival. We then overexpressed miR-449b by miRNA mimic transfection and inhibited miR-449b by miRNA antisense transfection. Cell growth was analyzed by CCK-8 assay and MTT assay, and apoptosis and cell proliferation were analyzed by flow cytometry. Overexpression of miR-449b significantly inhibited cell growth, while depletion of miR-449b increased cell growth. Moreover, the effects of miR-449b on cell growth were through modulation of cell proliferation rather than through modulation of cell apoptosis. Targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay, showing that miR-449b binds to the 3'-UTR of MET (hepatocyte growth factor receptor) mRNA, to inhibit its expression in TC cells. MET levels were regulated by miR-449b in TT cells. Together, we show that reduced miR-449b levels in TT tissues may promote TC growth, through MET-mediated cell proliferation.

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“…Also, as shown in Figure 2, HGF alone evidently increased the number and size of the cell colonies; however, cotreatment with HGF and SAIT301 decreased the number and size of colonies of HNE1 cells. Similar to our results, Li et al 35 reported that knockdown of Met using siRNA inhibits the survival, proliferation and invasion of NPC cells. Zhou et al 24 demonstrated that HGF, which is involved in the invasive phenotype and motility of NPC cells, is mediated by JNK through upregulation of MMP-9.…”

Section: Po005 Versus Hgf-treated Cells)supporting

confidence: 93%

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

Kim¹,

Lee²,

Kim³

et al. 2014

European Journal of Cancer

0

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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.

show abstract

Silencing of c-Met by RNA interference inhibits the survival, proliferation, and invasion of nasopharyngeal carcinoma cells

Cited by 15 publications

References 31 publications

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

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

Regulation of MET-mediated proliferation of thyroid carcinoma cells by miR-449b

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

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