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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

Immunohistochemical analysis of E-cadherin (A) and Slug (B) expression in patient samplesSamples were obtained from patients with mild, moderate or severe dysplasia and invasive cervical carcinoma. LSIL – Low-grade squamous Intraepithelial Lesion, HSIL – High-grade squamous Intraepithelial Lesion (according to Bethesda system terminology). **p < 0.001; # p < 0.05.
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Figure 6: Immunohistochemical analysis of E-cadherin (A) and Slug (B) expression in patient samplesSamples were obtained from patients with mild, moderate or severe dysplasia and invasive cervical carcinoma. LSIL – Low-grade squamous Intraepithelial Lesion, HSIL – High-grade squamous Intraepithelial Lesion (according to Bethesda system terminology). **p < 0.001; # p < 0.05.

Mentions: Immunohistochemical study of 37 patients' samples showed low E-cadherin expression in high-grade intraepithelial lesion (HSIL) and invasive carcinoma Figure 6A. To our surprise, a significant decrease in the E-cadherin was also observed for low-grade squamous intraepithelial lesion (LSIL) in comparison to normal cervix (Figure 6A, Supplementary Table 2). Slug expression was higher in HSIL and invasive carcinoma in comparison to LSIL (Figure 6B; Supplementary Table 3).


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)

Immunohistochemical analysis of E-cadherin (A) and Slug (B) expression in patient samplesSamples were obtained from patients with mild, moderate or severe dysplasia and invasive cervical carcinoma. LSIL – Low-grade squamous Intraepithelial Lesion, HSIL – High-grade squamous Intraepithelial Lesion (according to Bethesda system terminology). **p < 0.001; # p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Immunohistochemical analysis of E-cadherin (A) and Slug (B) expression in patient samplesSamples were obtained from patients with mild, moderate or severe dysplasia and invasive cervical carcinoma. LSIL – Low-grade squamous Intraepithelial Lesion, HSIL – High-grade squamous Intraepithelial Lesion (according to Bethesda system terminology). **p < 0.001; # p < 0.05.
Mentions: Immunohistochemical study of 37 patients' samples showed low E-cadherin expression in high-grade intraepithelial lesion (HSIL) and invasive carcinoma Figure 6A. To our surprise, a significant decrease in the E-cadherin was also observed for low-grade squamous intraepithelial lesion (LSIL) in comparison to normal cervix (Figure 6A, Supplementary Table 2). Slug expression was higher in HSIL and invasive carcinoma in comparison to LSIL (Figure 6B; Supplementary Table 3).

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