ARHGAP12 and ARHGAP29 exert distinct regulatory effects on switching between two cell morphological states through GSK-3 activity

• DOI: 10.1016/j.celrep.2025.115361
• Publication Date: 2025-03-06T01:05:25Z
• Authors: Vinton W.T. Cheng; Philippa Vaughn-B...; Gary C. Shaw; Malte Kriegs; Alastair Droop; George Psakis; Michel Mittelbronn; Matt Humphries; Filomena Esteves; Josie Hayes; Julia V. Cockle; Sabine Knipp; Arndt Rohwedder; Azzam Ismail; Ola Rominiyi; Spencer J. Collis; Georgia Mavria; James Samarasekara; John E. Ladbury; Sophie Ketchen; Ruth Morton; Sarah Fagan; Daniel Tams; Katie Myers; Connor McGarrity-...; Mark Dunning; Marjorie Boissinot; George Michalopoulos; Sally Prior; Yun Wah Lam; Ewan E. Morrison; Susan C. Short; Sean E. Lawler; Anke Brüning-Rich...

Cancer cells undergo morphological changes and phenotype switching to promote invasion into healthy tissues. Manipulating the transitional states in cancer prevent tumor dissemination may enhance survival improve treatment response. We describe two members of RhoGTPase activating protein (ARHGAP) family, ARHGAP12 ARHGAP29, as regulators glioma via Src kinase signaling events, leading that correspond switching. Moreover, we establish a link between glycogen synthase 3 (GSK-3) inhibition β-catenin translocation altering transcription ARHGAP29. Silencing causes loss N-cadherin adoption mesenchymal morphology, characteristic feature aggressive cellular behavior. In patients with glioblastoma (GBM), identify ARHGAP29 co-expression recurrence after treatment. Consequently, propose further investigation how ARHGAPs regulate events drive is warranted.