Back to Search
Start Over
YAP/TAZ-mediated regulation of laminin 332 is enabled by β4 integrin repression of ZEB1 to promote ferroptosis resistance.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2024 Apr; Vol. 300 (4), pp. 107202. Date of Electronic Publication: 2024 Mar 18. - Publication Year :
- 2024
-
Abstract
- We are interested in the contribution of integrins and the extracellular matrix to epithelial differentiation in carcinomas. This study was motivated by our finding that the Hippo effectors YAP and TAZ can sustain the expression of laminin 332 (LM332), the predominant ECM ligand for the integrin β4, in breast carcinoma cells with epithelial differentiation. More specifically, we observed that YAP and TAZ regulate the transcription of the LAMC2 subunit of LM332. Given that the β4-LM332 axis is associated with epithelial differentiation and YAP/TAZ have been implicated in carcinoma de-differentiation, we sought to resolve this paradox. Here, we observed that the β4 integrin sustains the expression of miR-200s that target the transcription factor ZEB1 and that ZEB1 has a pivotal role in determining the nature of YAP/TAZ-mediated transcription. In the presence of β4, ZEB1 expression is repressed enabling YAP/TAZ/TEAD-mediated transcription of LAMC2. The absence of β4, however, induces ZEB1, and ZEB1 binds to the LAMC2 promoter to inhibit LAMC2 transcription. YAP/TAZ-mediated regulation of LAMC2 has important functional consequences because we provide evidence that LM332 enables carcinoma cells to resist ferroptosis in concert with the β4 integrin.<br />Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Female
Humans
Breast Neoplasms metabolism
Breast Neoplasms pathology
Breast Neoplasms genetics
Cell Adhesion Molecules metabolism
Cell Adhesion Molecules genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
MicroRNAs metabolism
MicroRNAs genetics
Phosphoproteins metabolism
Phosphoproteins genetics
Trans-Activators metabolism
Trans-Activators genetics
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Signal Transducing genetics
Integrin beta4 metabolism
Integrin beta4 genetics
Kalinin metabolism
Transcriptional Coactivator with PDZ-Binding Motif Proteins metabolism
YAP-Signaling Proteins metabolism
Zinc Finger E-box-Binding Homeobox 1 metabolism
Zinc Finger E-box-Binding Homeobox 1 genetics
Ferroptosis
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 300
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38508310
- Full Text :
- https://doi.org/10.1016/j.jbc.2024.107202