Naslov
TWIST1 upregulation affects E-cadherin expression in brain metastases
(TWIST1 upregulation affects E-cadherin expression in brain metastases)

Autori
Brlek, Petar ; Bukovac, Anja ; Kafka, Anja ; Pećina-Šlaus, Nives

Izvornik
Clinical & Translational Oncology (1699-048X) 23 (2021); 1085-1095

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
metastasis ; brain ; epithelial-mesenchymal transition ; TWIST1 ; E-cadherin

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA