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MET receptor is a potential therapeutic target in high grade cervical cancer.

Miekus K, Pawlowska M, Sekuła M, Drabik G, Madeja Z, Adamek D, Majka M - Oncotarget (2015)

Bottom Line: MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis.Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype.Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.

ABSTRACT
Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype. Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma.

No MeSH data available.


Related in: MedlinePlus

Cell morphology and actin organization after MET silencingAn analysis of cell morphology revealed a decrease in cell size (A) and changes in F-actin organization (B) in MET-deficient HTB-35 cells. A – Cells were photographed with Nomarski interference contrast (upper panel) and analyzed with MIGRA software (lower panel). B – Immunofluorescence staining of the F-actin cytoskeleton shows re-organization of actin filaments from thick contractile bundles in control cells to thin cortical bundles – as in epithelial cells – in MET-deficient cells. Representative staining is shown. Bar = 50 μm., ## p < 0.005.
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Figure 5: Cell morphology and actin organization after MET silencingAn analysis of cell morphology revealed a decrease in cell size (A) and changes in F-actin organization (B) in MET-deficient HTB-35 cells. A – Cells were photographed with Nomarski interference contrast (upper panel) and analyzed with MIGRA software (lower panel). B – Immunofluorescence staining of the F-actin cytoskeleton shows re-organization of actin filaments from thick contractile bundles in control cells to thin cortical bundles – as in epithelial cells – in MET-deficient cells. Representative staining is shown. Bar = 50 μm., ## p < 0.005.

Mentions: MET receptor downregulation significantly affected the morphology of HTB-35 cells. After transduction with the shMET lentiviral vector, the cells became small and rounded, whereas control cells resembled fibroblast-like cells with an elongated shape (Figure 5A). The values for all cell morphology parameters (area, periphery, extension, dispersion and elongation) were significantly lower in HTB-35 shMET relative to control cells. The data are summarized in Table 1. We also observed that MET downregulation altered F-actin organization. In MET-deficient HTB-35 cells, F-actin was located under the cell membrane and did not form regular stress fibers as observed in WT and shLacZ cells. Actin filaments reorganized from thick, parallel, contractile bundles in control cells to thin cortical bundles – as in epithelial cells – in MET-deficient cells (Figure 5B).


MET receptor is a potential therapeutic target in high grade cervical cancer.

Miekus K, Pawlowska M, Sekuła M, Drabik G, Madeja Z, Adamek D, Majka M - Oncotarget (2015)

Cell morphology and actin organization after MET silencingAn analysis of cell morphology revealed a decrease in cell size (A) and changes in F-actin organization (B) in MET-deficient HTB-35 cells. A – Cells were photographed with Nomarski interference contrast (upper panel) and analyzed with MIGRA software (lower panel). B – Immunofluorescence staining of the F-actin cytoskeleton shows re-organization of actin filaments from thick contractile bundles in control cells to thin cortical bundles – as in epithelial cells – in MET-deficient cells. Representative staining is shown. Bar = 50 μm., ## p < 0.005.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496342&req=5

Figure 5: Cell morphology and actin organization after MET silencingAn analysis of cell morphology revealed a decrease in cell size (A) and changes in F-actin organization (B) in MET-deficient HTB-35 cells. A – Cells were photographed with Nomarski interference contrast (upper panel) and analyzed with MIGRA software (lower panel). B – Immunofluorescence staining of the F-actin cytoskeleton shows re-organization of actin filaments from thick contractile bundles in control cells to thin cortical bundles – as in epithelial cells – in MET-deficient cells. Representative staining is shown. Bar = 50 μm., ## p < 0.005.
Mentions: MET receptor downregulation significantly affected the morphology of HTB-35 cells. After transduction with the shMET lentiviral vector, the cells became small and rounded, whereas control cells resembled fibroblast-like cells with an elongated shape (Figure 5A). The values for all cell morphology parameters (area, periphery, extension, dispersion and elongation) were significantly lower in HTB-35 shMET relative to control cells. The data are summarized in Table 1. We also observed that MET downregulation altered F-actin organization. In MET-deficient HTB-35 cells, F-actin was located under the cell membrane and did not form regular stress fibers as observed in WT and shLacZ cells. Actin filaments reorganized from thick, parallel, contractile bundles in control cells to thin cortical bundles – as in epithelial cells – in MET-deficient cells (Figure 5B).

Bottom Line: MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis.Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype.Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.

ABSTRACT
Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype. Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma.

No MeSH data available.


Related in: MedlinePlus