TWIST1 upregulation affects E-cadherin expression in brain metastases

Znanstveni rad - Izvorni znanstveni rad

• Autor: Petar Brlek
• Autor: Anja Bukovac
• Autor: Anja Kafka
• Autor: Nives Pećina-Šlaus
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA MEDICINSKU BIOLOGIJU)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Neuroznanost

Sažetak (engleski)

Purpose: 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.
-----
Methods: 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.
-----
Results: 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).
-----
Conclusion: 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.

• Ključne riječi (engleski): Adult; Aged; Aged, 80 and over; Brain Neoplasms / metabolism*; Brain Neoplasms / secondary*; Breast Neoplasms / pathology*; Cadherins / biosynthesis*; Female; Humans; Lung Neoplasms / pathology*; Male; Middle Aged; Nuclear Proteins / physiology*; Twist-Related Protein 1 / physiology*; Up-Regulation*
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Završna verzija rukopisa prihvaćena za objavljivanje (postprint)
• Naslov časopisa: Clinical and Translational Oncology
• Brojčani podaci: vol. 23, br. 6, str. 1085-1095
• p-ISSN: 1699-048X
• e-ISSN: 1699-3055
• DOI: https://doi.org/10.1007/s12094-020-02496-3
• URN:NBN: urn:nbn:hr:105:272246
• Datum objave publikacije: 2021-06
• URL dokumenta: https://link.springer.com/10.1007/s12094-020-02496-3
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup; Datum isteka embarga: 2022-07-01
• Datum i vrijeme pohrane: 2022-02-07 10:12:03