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TWIST1 upregulation affects E-cadherin expression in brain metastases

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Bibliographic Details
Title: TWIST1 upregulation affects E-cadherin expression in brain metastases
Authors: P. Brlek, A. Bukovac, A. Kafka, N. Pećina-Šlaus
Source: Clinical and Translational Oncology. 23:1085-1095
Publisher Information: Springer Science and Business Media LLC, 2020.
Publication Year: 2020
Subject Terms: Adult, Male, 0301 basic medicine, Lung Neoplasms, brain, Nuclear Proteins / physiology, epithelial-mesenchymal transition, TWIST1, Breast Neoplasms, Cadherins / biosynthesis, Lung Neoplasms / pathology, 03 medical and health sciences, 0302 clinical medicine, metastasis, Humans, Aged, Aged, 80 and over, Brain Neoplasms, Twist-Related Protein 1, E-cadherin, Nuclear Proteins, Breast Neoplasms / pathology, Middle Aged, Cadherins, Twist-Related Protein 1 / physiology, Up-Regulation, Brain Neoplasms / secondary, Brain Neoplasms / metabolism, Female
Description: E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal transition (EMT)-a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites-breast and lung.The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin-horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations.Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p = 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p = 0.034).This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment.
Document Type: Article
File Description: application/pdf
Language: English
ISSN: 1699-3055
1699-048X
DOI: 10.1007/s12094-020-02496-3
Access URL: https://pubmed.ncbi.nlm.nih.gov/33006113
https://europepmc.org/article/MED/33006113
https://www.bib.irb.hr/1084640
https://www.ncbi.nlm.nih.gov/pubmed/33006113
https://link.springer.com/article/10.1007/s12094-020-02496-3
https://pubmed.ncbi.nlm.nih.gov/33006113/
https://dialnet.unirioja.es/servlet/articulo?codigo=7898917
Rights: Springer TDM
URL: http://rightsstatements.org/vocab/InC/1.0/
Accession Number: edsair.doi.dedup.....cb5d91b3fff23ecb4392c81740e70b1f
Database: OpenAIRE
Description
Abstract:E-cadherin is a calcium-dependent glycoprotein whose main role is cell-cell adhesion. Its transcriptional repressor TWIST1 is a basic helix-loop-helix (bHLH) protein that participates in gastrulation and formation of mesodermal tissues during embryogenesis. In adult tissues, the high expression of TWIST1 induces the epithelial-mesenchymal transition (EMT)-a process in which cells become motile and able to metastasize. In this paper, we investigated the involvement of E-cadherin and TWIST1 in the carcinogenesis of brain metastases originating from two different primary sites-breast and lung.The localization and expression of E-cadherin and its transcriptional repressor TWIST1 were investigated using a DAB-labeled streptavidin-horseradish peroxidase immunohistochemical reaction and specific monoclonal antibodies against TWIST1 and E-cadherin. Image J software was used for semi-quantitative analysis while H-score served for statistical evaluations.Immunohistochemistry showed that the expression of E-cadherin was downregulated in 85.7% of brain metastases, while at the same time, 82.2% of them showed upregulated TWIST1. Statistical analysis confirmed a significant negative correlation between expressions of TWIST1 and E-cadherin (p = 0.001). When the brain metastases expression levels were compared to primary breast tumors in corresponding patients, E-cadherin showed higher expression in primary pairs compared to corresponding metastases. Consistent to its role, TWIST1 was downregulated in all primary tumor samples in comparison to corresponding metastases pairs (p = 0.034).This research provides valuable data regarding molecular events involving two EMT key components that could give directions for new possibilities for brain metastases diagnosis and treatment.
ISSN:16993055
1699048X
DOI:10.1007/s12094-020-02496-3