Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation

Awano, Shuji; Dawson, Louise A.; Hunter, Alison R.; Turner, Anthony J.; Usmani, Badar A.

doi:10.1002/ijc.21525

Cited by 37 publications

(43 citation statements)

References 54 publications

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“…Elevated ECE-1 levels are increasingly being correlated with tumour progression in PC and other types of malignancies (Egidy et al, 2000b;Arun et al, 2001;Dawson et al, 2004Dawson et al, , 2006Awano et al, 2005;Smollich et al, 2007). We have previously recognised the ability of ECE-1 to promote PC cell invasion in vitro (Dawson et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Although ECE-1 has been reported in a number of cancers (Ahmed et al, 2000;Egidy et al, 2000aEgidy et al, , 2000bArun et al, 2001;Usmani et al, 2002;Dawson et al, 2004Dawson et al, , 2006Awano et al, 2005;Smollich et al, 2007), specific isoforms present have yet to be identified. To our knowledge, ECE-1a expression has not been reported in any cancer cells either in vitro or in vivo, and only ECE-1c is abundant in prostate and lung cancer (Ahmed et al, 2000;Dawson et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Endothelin-1 is generated from its inactive precursor big ET-1 by endothelin-converting enzyme 1 (ECE-1). We and others have shown that ECE-1 expression is significantly elevated in tumours (Ahmed et al, 2000;Eberl et al, 2000;Egidy et al, 2000b;Arun et al, 2001;Usmani et al, 2002;Dawson et al, 2004Dawson et al, , 2006Awano et al, 2005;Smollich et al, 2007). We have previously demonstrated that ECE-1 is present in PC cell lines and primary tissues, and is expressed at the cell surface and intracellularly (Dawson et al, 2004(Dawson et al, , 2006, with levels of ECE-1 elevated in primary malignant stromal cells as compared with benign (Dawson et al, 2004).…”

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confidence: 89%

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Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

et al. 2008

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Cross-talk between tumour and stromal cells can profoundly influence cancer cell invasion by increasing the availability of mitogenic peptides such as endothelin-1 (ET-1). Endothelin-1 is elevated in men with metastatic prostate cancer (PC), and can exert both an autocrine (epithelial) and a paracrine (stromal) influence on growth. Endothelin-1 is generated from its inactive precursor big-ET-1 by endothelin-converting enzyme 1 (ECE-1). We and others have demonstrated that ECE-1 expression is significantly elevated in tumours and surrounding stromal tissue. Our current data show siRNA-mediated knockdown of stromal ECE-1 reduces epithelial (PC-3) cell invasion in coculture. Interestingly, readdition of ET-1 only partially recovers this effect suggesting a novel role for ECE-1 independent of ET-1 activation. Parallel knockdown of ECE-1 in both stromal and epithelial compartments results in an additive decrease in cell invasion. We extrapolated this observation to the four recognised isoforms ECE-1a, ECE-1b, ECE-1c and ECE-1d. Only ECE-1a and ECE-1c were significant but with reciprocal effects on cell invasion. Transient ECE-1c overexpression increased PC-3 invasiveness through matrigel, whereas transient ECE-1a expression suppressed invasion. Furthermore, transient ECE-1a expression in stromal cells strongly counteracts the effect of transient ECE-1c expression in PC-3 cells. The ECE-1 isoforms may, therefore, be relevant targets for antiinvasive therapy in prostate and other cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

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Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

et al. 2008

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“…Interestingly, it was reported that breast cancer patients with ECE-1-overexpressing tumors had more frequent disease recurrence and that ECE-1 inhibition, using an enzyme inhibitor, in MCF-7 breast cancer cells led to significantly decreased ET-1 expression and reduced cell invasiveness (55). In addition, decreased ECE-1 expression, following ECE siRNA treatment, reduced ET-1-dependent oral squamous carcinoma cell proliferation (56). These reports support the approach proposed here, indicating that ECE-1 is a potential target for siRNA-mediated treatment of ovarian and other cancers either by i.p.…”

Section: Discussionmentioning

confidence: 99%

Small Interfering RNA Molecules Targeting Endothelin-Converting Enzyme-1 Inhibit Endothelin-1 Synthesis and the Invasive Phenotype of Ovarian Carcinoma Cells

et al. 2008

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Endothelin-1 (ET-1) has been implicated in the progression of various cancers, including ovarian carcinoma. We found that the ovarian carcinoma cell lines ES2 and OVCAR3 and tumors from different anatomic sites expressed ET-1 system members [ET receptor A and ET-converting enzyme-1 (ECE-1)]. However, only ECE-1 was significantly higher in the solid tumors compared with effusions. We therefore investigated the effect of RNA interference-induced knockdown of ECE-1, the key enzyme in ET-1 production, on these two ovarian carcinoma cell lines. Small interfering RNA (siRNA) targeting of ECE-1 markedly reduced ECE-1 mRNA and protein levels, which subsequently led to 80% to 90% inhibition of ET-1 peptide secretion by the cells. ECE-1 silencing also profoundly affected the behavior of tumor cells compared with cells treated with scrambled siRNA. Silenced cells exhibited (a) reduced ET-1-dependent p44/42 mitogen-activated protein kinase phosphorylation; (b) decreased invasiveness and matrix metalloproteinase-2 activity; (c) improved adhesion to basal lamina proteins, laminin-1, and collagen IV; and (d) increased Ecadherin, an epithelial adhesion molecule, and reduced Ncadherin expression, a mesenchymal marker. Altered cell adherence is one of the hallmarks of the transformed phenotype, often characterized by the loss of the epithelial features and the gain of a mesenchymal phenotype. ECE-1 ablation did not, however, alter viable ovarian carcinoma cell numbers. Addition of exogenous ET-1 reversed the effects cited above. Taken together, these data indicate that siRNA is an effective tool for manipulating ECE-1 expression, ET-1 biosynthesis, and invasiveness of ovarian carcinoma. ECE-1 silencing may therefore develop into a promising novel anticancer therapy. [Cancer Res 2008;68(22):9265-73]

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“…As per the data available, it has been concluded that ET-1, its receptor-endothelin receptor A and B are overexpressed in OSCC, where in ET-1 mediates cell growth and proliferation [65]. ET-1, in the oral cavity, is also responsible for stimulating the release of ADAM17, a bioactive ligand, from fibroblast which is followed by its interaction with cell surface receptor-EGFR on the cancer cells, thereby increasing the cancer cell migration as well as invasion [66,67].…”

Section: Endothelin 1 and Its Role In Oral Carcinogenesismentioning

confidence: 99%

Oral Cancer Biomarkers - as Powerful Diagnostic and Prognostic Tools

Ahuja¹

2016

Int.J.Curr.Microbiol.App.Sci

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Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation

Cited by 37 publications

References 54 publications

Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

Small Interfering RNA Molecules Targeting Endothelin-Converting Enzyme-1 Inhibit Endothelin-1 Synthesis and the Invasive Phenotype of Ovarian Carcinoma Cells

Oral Cancer Biomarkers - as Powerful Diagnostic and Prognostic Tools

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