RRC ID 78626
Author Kobayashi Y, Yokoi A, Hashimura M, Oguri Y, Konno R, Matsumoto T, Tochimoto M, Nakagawa M, Ishibashi Y, Ito T, Ohhigata K, Harada Y, Fukagawa N, Kodera Y, Saegusa M.
Title Nucleobindin-2 Mediates Transforming Growth Factor-β1-Driven Phenotypes in Zinc Finger E-Box Binding Homeobox 1-High Uterine Carcinosarcoma.
Journal Am J Pathol
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.
Volume 193(8)
Pages 1116-1128
Published 2023-8-1
DOI 10.1016/j.ajpath.2023.04.011
PII S0002-9440(23)00168-2
PMID 37169340
MeSH Cadherins / genetics Cadherins / metabolism Carcinosarcoma* / genetics Carcinosarcoma* / pathology Cell Line, Tumor Epithelial-Mesenchymal Transition / genetics Female Genes, Homeobox Humans Nucleobindins / genetics Nucleobindins / metabolism Phenotype Transforming Growth Factor beta1 / metabolism Uterine Neoplasms* / genetics Uterine Neoplasms* / pathology Vimentin / metabolism Zinc Finger E-box-Binding Homeobox 1 / genetics Zinc Finger E-box-Binding Homeobox 1 / metabolism Zinc Fingers
Human and Animal Cells JHUCS-1(RCB1547)