TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer

Tumor budding in colorectal cancer is likened to an epithelial-mesenchymal transition (EMT) characterized predominantly by loss of E-cadherin and up-regulation of E-cadherin repressors like TWIST1 and TWIST2. Here we investigate a possible epigenetic link between TWIST proteins and the tumor budding...

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Main Authors:	Galván, José A., Helbling, Melina, Koelzer, Viktor H., Tschan, Mario P., Berger, Martin D., Hädrich, Marion, Schnüriger, Beat, Karamitopoulou, Eva, Dawson, Heather, Inderbitzin, Daniel, Lugli, Alessandro, Zlobec, Inti
Format:	Online
Language:	English
Published:	Impact Journals LLC 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359262/

id	pubmed-4359262
recordtype	oai_dc
spelling	pubmed-43592622015-03-27 TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer Galván, José A. Helbling, Melina Koelzer, Viktor H. Tschan, Mario P. Berger, Martin D. Hädrich, Marion Schnüriger, Beat Karamitopoulou, Eva Dawson, Heather Inderbitzin, Daniel Lugli, Alessandro Zlobec, Inti Research Paper Tumor budding in colorectal cancer is likened to an epithelial-mesenchymal transition (EMT) characterized predominantly by loss of E-cadherin and up-regulation of E-cadherin repressors like TWIST1 and TWIST2. Here we investigate a possible epigenetic link between TWIST proteins and the tumor budding phenotype. TWIST1 and TWIST2 promoter methylation and protein expression were investigated in six cell lines and further correlated with tumor budding in patient cohort 1 (n = 185). Patient cohort 2 (n = 112) was used to assess prognostic effects. Laser capture microdissection (LCM) of tumor epithelium and stroma from low- and high-grade budding cancers was performed. In colorectal cancers, TWIST1 and TWIST2 expression was essentially restricted to stromal cells. LCM results of a high-grade budding case show positive TWIST1 and TWIST2 stroma and no methylation, while the low-grade budding case was characterized by negative stroma and strong hypermethylation. TWIST1 stromal cell staining was associated with adverse features like more advanced pT (p = 0.0044), lymph node metastasis (p = 0.0301), lymphatic vessel invasion (p = 0.0373), perineural invasion (p = 0.0109) and worse overall survival time (p = 0.0226). Stromal cells may influence tumor budding in colorectal cancers through expression of TWIST1. Hypermethylation of the tumor stroma may represent an alternative mechanism for regulation of TWIST1. Impact Journals LLC 2014-11-26 /pmc/articles/PMC4359262/ /pubmed/25528769 Text en Copyright: © 2015 Galván et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Galván, José A. Helbling, Melina Koelzer, Viktor H. Tschan, Mario P. Berger, Martin D. Hädrich, Marion Schnüriger, Beat Karamitopoulou, Eva Dawson, Heather Inderbitzin, Daniel Lugli, Alessandro Zlobec, Inti
spellingShingle	Galván, José A. Helbling, Melina Koelzer, Viktor H. Tschan, Mario P. Berger, Martin D. Hädrich, Marion Schnüriger, Beat Karamitopoulou, Eva Dawson, Heather Inderbitzin, Daniel Lugli, Alessandro Zlobec, Inti TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
author_facet	Galván, José A. Helbling, Melina Koelzer, Viktor H. Tschan, Mario P. Berger, Martin D. Hädrich, Marion Schnüriger, Beat Karamitopoulou, Eva Dawson, Heather Inderbitzin, Daniel Lugli, Alessandro Zlobec, Inti
author_sort	Galván, José A.
title	TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
title_short	TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
title_full	TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
title_fullStr	TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
title_full_unstemmed	TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
title_sort	twist1 and twist2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer
description	Tumor budding in colorectal cancer is likened to an epithelial-mesenchymal transition (EMT) characterized predominantly by loss of E-cadherin and up-regulation of E-cadherin repressors like TWIST1 and TWIST2. Here we investigate a possible epigenetic link between TWIST proteins and the tumor budding phenotype. TWIST1 and TWIST2 promoter methylation and protein expression were investigated in six cell lines and further correlated with tumor budding in patient cohort 1 (n = 185). Patient cohort 2 (n = 112) was used to assess prognostic effects. Laser capture microdissection (LCM) of tumor epithelium and stroma from low- and high-grade budding cancers was performed. In colorectal cancers, TWIST1 and TWIST2 expression was essentially restricted to stromal cells. LCM results of a high-grade budding case show positive TWIST1 and TWIST2 stroma and no methylation, while the low-grade budding case was characterized by negative stroma and strong hypermethylation. TWIST1 stromal cell staining was associated with adverse features like more advanced pT (p = 0.0044), lymph node metastasis (p = 0.0301), lymphatic vessel invasion (p = 0.0373), perineural invasion (p = 0.0109) and worse overall survival time (p = 0.0226). Stromal cells may influence tumor budding in colorectal cancers through expression of TWIST1. Hypermethylation of the tumor stroma may represent an alternative mechanism for regulation of TWIST1.
publisher	Impact Journals LLC
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359262/
_version_	1613198491474984960

TWIST1 and TWIST2 promoter methylation and protein expression in tumor stroma influence the epithelial-mesenchymal transition-like tumor budding phenotype in colorectal cancer

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