Loss of E-cadherin and Acquisition of Vimentin in Epithelial-Mesenchymal Transition are Noble Indicators of Uterine Cervix Cancer Progression

Abstract

BackgroundEpithelial-mesenchymal transition (EMT) has been known to play a key role in the stromal invasion of carcinoma in situ (CIS) lesion. Loss of E-cadherin and acquisition of vimentin are two critical steps in EMT, that are induced by Snail-1 upregulation associated with overexpression of epidermal growth factor receptor (EGFR). However, roles of EMT-related proteins in human cervical tissues have not been fully elucidated. In this study, we investigated the immunoexpressions of EMT-related proteins in CIS, microinvasive squamous cell carcinoma (SCC), and invasive SCC to demonstrate their key roles in tumor progression.MethodsEighty one CIS, 17 microinvasive, and 21 invasive SCC cases were immunostained with primary antibodies for Snail-1, EGFR, E-cadherin, and vimentin on paraffin-embedded tissue microarray blocks.ResultsEGFR and Snail-1 proteins were highly expressed but the levels were not significantly different between the three groups. However, loss of E-cadherin and acquisition of vimentin were proven to occur significantly higher in microinvasive and invasive SCC cases than in CIS.ConclusionsE-cadherin and vimentin were found to be two useful indicators of EMT in evaluating stromal invasion of CIS. However, it was not demonstrated for Snail-1 and EGFR proteins to play any key role in the progression of cervix cancer.

Astrocyte Elevated Gene-1 Promotes Progression of Cervical Squamous Cell Carcinoma by Inducing Epithelial-Mesenchymal Transition via Wnt Signaling

“…EGFR has been found to be overexpressed in cervical cancer 23 and to be an important inducer of EMT. 24,25 EGFR activation up-regulates Snail expression to promote EMT and progression of cervical cancer. 26 Another important tyrosine kinase receptor is EphB2, the activation of which is recently demonstrated to promote EMT through Ras signal pathway in cervical cancer.…”

Prognostic significance of YY1 protein expression and mRNA levels by bioinformatics analysis in human cancers: A therapeutic target

“…Cells undergoing EMT lose epithelial markers such as E-cadherin and gain mesenchymal markers such as vimentin and fibronectin. The constitutively-activated NF-κB pathway in tumors has been reported to be involved in the EMT switch through the regulation of target genes, such as Snail family members, that result in the repression of E-cadherin (Myong, 2012). Our findings with the dysregulated NF-κB/Snail/YY1/RKIP loop in cancer suggested that each member of this loop would be also involved in the regulation of EMT, particularly since YY1 regulates Snail and Snail is directly involved in EMT (Bonavida & Baritaki, 2011a, 2011b.…”

Epithelial–mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy

“…In particular, HPV E6 oncoprotein expression induces characteristic changes in EMT 32. Myong and collaborators showed that the loss of E‐cadherin and gain of vimentin are found within more aggressive cervical‐derived invasive lesions but not within preneoplastic alterations 33. Our results suggest that the presence of EMT markers negatively affected women with locally advanced CC.…”