Cheng, V.W.T., Vaughn-Beaucaire, P., Shaw, G.C. et al. (31 more authors) (2025) ARHGAP12 and ARHGAP29 exert distinct regulatory effects on switching between two cell morphological states through GSK-3 activity. Cell Reports, 44 (3). 115361. ISSN 2639-1856
Abstract
Cancer cells undergo morphological changes and phenotype switching to promote invasion into healthy tissues. Manipulating the transitional morphological states in cancer cells to prevent tumor dissemination may enhance survival and improve treatment response. We describe two members of the RhoGTPase activating protein (ARHGAP) family, ARHGAP12 and ARHGAP29, as regulators of transitional morphological states in glioma via Src kinase signaling events, leading to morphological changes that correspond to phenotype switching. Moreover, we establish a link between glycogen synthase kinase 3 (GSK-3) inhibition and β-catenin translocation in altering transcription of ARHGAP12 and ARHGAP29. Silencing ARHGAP12 causes loss of N-cadherin and adoption of mesenchymal morphology, a characteristic feature of aggressive cellular behavior. In patients with glioblastoma (GBM), we identify a link between ARHGAP12 and ARHGAP29 co-expression and recurrence after treatment. Consequently, we propose that further investigation of how ARHGAPs regulate transitional morphological events to drive cancer dissemination is warranted.
Metadata
Item Type: | Article |
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Authors/Creators: | This paper has 34 authors. You can scroll the list below to see them all or them all.
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Copyright, Publisher and Additional Information: | © 2025 Published by Elsevier Inc. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY-NC-ND 4.0). |
Keywords: | glioma, RhoGTPase activating protein, glycogen synthase kinase 3, cell morphology, Src kinase signaling, tumor recurrence, BIO-indirubin |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 24 Mar 2025 10:42 |
Last Modified: | 24 Mar 2025 10:42 |
Status: | Published |
Publisher: | Cell Press |
Identification Number: | 10.1016/j.celrep.2025.115361 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224701 |