Back to Search
Start Over
Nucleobindin-2 Mediates Transforming Growth Factor-β1-Driven Phenotypes in Zinc Finger E-Box Binding Homeobox 1-High Uterine Carcinosarcoma.
- Source :
-
The American journal of pathology [Am J Pathol] 2023 Aug; Vol. 193 (8), pp. 1116-1128. Date of Electronic Publication: 2023 May 09. - Publication Year :
- 2023
-
Abstract
- Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, shotgun proteomics analysis used to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS indicated up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells. NUCB2 knockout reduced cell proliferation and migration, whereas NUCB2 overexpression had the opposite effect. Treatment of Em Ca cells with transforming growth factor (TGF)-β1 dramatically altered morphology toward a fibroblastic appearance; concomitantly, expression of NUCB2 and ZEB1 increased. The NUCB2 promoter was also activated by transfection of Smad2. In UCS tissues, NUCB2 expression was significantly higher in sarcomatous compared with carcinomatous components, which was consistent with increased TGF-β1 mRNA expression in stromal and sarcomatous components compared with carcinomatous components. In addition, NUCB2 score correlated positively with ZEB1 and vimentin scores, whereas ZEB1 score correlated positively with Slug and vimentin scores and inversely with the E-cadherin score. Collectively, these data indicate that TGF-β-dependent up-regulation of NUCB2 and ZEB1 contributes to the phenotypic characteristics of sarcomatous components in UCS.<br /> (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Female
Zinc Finger E-box-Binding Homeobox 1 genetics
Zinc Finger E-box-Binding Homeobox 1 metabolism
Nucleobindins genetics
Nucleobindins metabolism
Transforming Growth Factor beta1 metabolism
Vimentin metabolism
Genes, Homeobox
Cadherins genetics
Cadherins metabolism
Phenotype
Zinc Fingers
Epithelial-Mesenchymal Transition genetics
Cell Line, Tumor
Uterine Neoplasms genetics
Uterine Neoplasms pathology
Carcinosarcoma genetics
Carcinosarcoma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 193
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 37169340
- Full Text :
- https://doi.org/10.1016/j.ajpath.2023.04.011