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Vascular endothelial growth factors (VEGFs) consist of five molecules (VEGFA through D as well as placental growth factor) which are crucial for regulating key cellular and tissue functions. The role of VEGF and its intracellular signaling and downstream molecular pathways have been thoroughly studied. Activation of VEGF signal transduction can be initiated by the molecules' binding to two classes of transmembrane receptors: (1) the VEGF tyrosine kinase receptors (VEGF receptors 1 through 3) and (2) the neuropilins (NRP1 and 2). The involvement of Rho GTPases in modulating VEGFA signaling in both cancer cells and endothelial cells has also been well established. Additionally, different isoforms of Rho GTPases, namely, RhoA, RhoC, and RhoG, have been shown to regulate VEGF expression as well as blood vessel formation. This review article will explore how Rho GTPases modulate VEGF signaling and the consequences of such interaction on cancer progression.
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http://dx.doi.org/10.1155/2020/2097214 | DOI Listing |
Bioessays
September 2025
MY Small G Protein Research Group, Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
Advanced biosensing technologies, such as Förster resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET), have enabled real-time, high-resolution tracking of Rho GTPase activity, surpassing traditional methods like pull-down assays. However, current biosensors mainly detect the GTP-bound active state through effector interactions, without directly measuring Rho GTPase expression or identifying related biomarkers of abnormal activation. Small Rho GTPases are essential molecular switches that regulate key cellular processes such as cytoskeletal organization, cell movement, polarity, vesicle trafficking, and the cell cycle.
View Article and Find Full Text PDFBiomed Pharmacother
September 2025
Pharmaceutical Biochemistry and Bioanalytics, Pharmaceutical Institute, University of Bonn, Bonn 53121, Germany. Electronic address:
Heterotrimeric G proteins are pivotal signal transduction molecules that propagate extracellular signals through G protein-coupled receptors (GPCRs) in the cell. Receptor activation initiates diverse signaling cascades depending on the associated G protein, particularly its Gα subunit, which determines assignment to either the Gαs/olf, Gαi/o, Gαq/11, or Gα12/13 family. The downstream signaling pathways of the families Gαs/olf, Gαi/o, and Gαq/11 have been explored to a greater extent than Gα12/13.
View Article and Find Full Text PDFCell Chem Biol
September 2025
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China; Centre for Oncology and Im
RhoA is a key cancer driver and potential colorectal cancer (CRC) therapy target but remains undrugged clinically. Using activity-based protein profiling (ABPP) and mass spectrometry (MS), we identified CL16, a covalent inhibitor targeting the unique Cys16 on RhoA subfamily, which confers high specificity over other Rho family proteins. Cys16 is adjacent to the nucleotide-binding pocket and switch regions, which are critical for RhoA function.
View Article and Find Full Text PDFSci Adv
September 2025
School of Engineering and Materials Science, Queen Mary University of London, UK.
During heart disease, the cardiac extracellular matrix (ECM) undergoes a structural and mechanical transformation. Cardiomyocytes sense the mechanical properties of their environment, leading to phenotypic remodeling. A critical component of the ECM mechanosensing machinery, including the protein talin, is organized at the cardiomyocyte costamere.
View Article and Find Full Text PDFGenet Res (Camb)
September 2025
Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.
Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer-related mortality worldwide. However, the expression and role of TIPE3 and RAC1 in LUAD are not well characterized. This study aimed to investigate the expression and clinicopathological significance of TNFAIP8L3 (TIPE3) and RAC1 in LUAD, as well as the relationship between these two proteins.
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