ZEB1 is neither sufficient nor required for epithelial-mesenchymal transition in LS174T colorectal cancer cells.
Biochem Biophys Res Commun
; 482(4): 1226-1232, 2017 Jan 22.
Article
en En
| MEDLINE
| ID: mdl-27923654
ABSTRACT
Epithelial-mesenchymal transition (EMT) is implicated in metastases formation and acquired therapy resistance in several tumor entities. The two transcription factors SNAIL1 and ZEB1 are thought to be master regulators of EMT and to form a core regulatory network required for EMT-associated transcriptional reprogramming. Yet, inducible EMT models show the sequential upregulation first of SNAIL1 and only subsequently of ZEB1. Therefore, SNAIL1 and ZEB1 might be differentially needed for the onset and propagation of EMT. Here we used LS174T colorectal adenocarcinoma cells which do not express endogenous EMT-inducing transcription factors, to investigate whether ZEB1 is an obligatory downstream mediator of Snail1-induced EMT, and to test whether ZEB1 could elicit an EMT in a background of naïve epithelial cells by itself. However, CRISPR/Cas9-mediated knockout of ZEB1 did not affect the ability of ectopically expressed Snail1 to trigger a complete EMT in ZEB1-deficient LS174T cells. In contrast to Snail1, ectopic ZEB1 had only minor effects on cell morphology and invasive growth in three-dimensional spheroid cultures. In agreement with this, expression of ZEB1 did not lead to repression of epithelial marker genes, and mesenchymal markers were not upregulated by ZEB1. Likewise, ectopic ZEB1 expression did not confer increased chemoresistance. We conclude that ZEB1 is neither required nor sufficient for EMT in LS174T colorectal cancer cells.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organoplatinos
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Neoplasias Colorrectales
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Regulación Neoplásica de la Expresión Génica
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Transición Epitelial-Mesenquimal
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Homeobox 1 de Unión a la E-Box con Dedos de Zinc
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2017
Tipo del documento:
Article
País de afiliación:
Alemania