Unravelling the roles of Vav3 in cytoskeletal control and angiogenesis

Abstract

The oncogene Vav guanine nucleotide exchange factor 3 (Vav3) can accelerate neovascularization in the context of cancer by increasing cell proliferation and metastasis, making it a useful reference for understanding the process of pannus development in rheumatoid arthritis (RA). The overactivation of synovial tissue leads to increased cell invasion and inflammatory infiltration, resulting in a tumour-like immune microenvironment. Pannus formation, an early complication of RA, can progress to bone injury. The regulatory effect of Vav3 on cell invasion mainly involves increased adhesion and metastasis to support neovascularization, with effects on inflammatory cells, osteoclasts, and the cytoskeleton, resulting in microvessel formation and even bone destruction. The influence of Vav3 on cell proliferation and differentiation manifests as the promotion of immune cell formation and activation, as well as the intensification of immune infiltration into the local tissue. Targeted inhibition of Vav3 expression can reduce the pathological damage described above and may be a potential therapeutic target to limit pannus formation. Notably, as Vav3 is a cytoskeleton-associated protein, the association between epigenetic modifications of Vav3 (such as methylation and acetylation) and metabolic reprogramming is an interesting direction for future research on autoimmune diseases. Therefore, we summarize the latest information related to the biological role of Vav3, emphasizing the regulatory effects of the cytoskeleton in pannus development in the context of tumour-related research and discussing the clinical value of Vav3 epigenetic modification and energy metabolism in angiogenesis.