Vav3 in Human Cancers: Mechanism and Clinical Implication Publisher Pubmed



Alhawary SIS¹ ; Alsalamy A² ; Gupta R³ ; Alsaab HO⁴ ; Hjazi A⁵ ; Edilboyev U⁶ ; Ramadan MF⁷ ; Hussien BM⁸ ; Ahmed M⁹ ; Hosseinifard SR¹⁰
Source: Pathology Research and Practice Published:2023

Abstract

Guanine nucleotide exchange factors (GEFs) are primarily involved in signal transmission between cell membrane receptors and intracellular mediators. Upon replacing GDP with GTP, GEFs can alter their conformation, resulting in their binding to downstream effectors, such as GTPases like Ras homologous (Rho). VAV GEF family are versatile proteins working as an adaptor mediator and GEF for Rho GTPase. They act as a phosphorylation-dependent molecular switcher, fluctuating between active (tyrosine phosphorylated) and inactive (non-phosphorylated) conformation in cell signaling. Accumulating data showed that VAV3 is implicated in cancer progression. The higher levels of VAV3 in human cancers proposed that it may have an oncogenic role in cancer progression. Available studies demonstrated that VAV3 promoted cell proliferation, epithelial-mesenchymal transition (EMT), colony formation, cell cycle, survival, migration and invasion, and suppressed cell apoptosis. In addition, other studies indicated that VAV3 may have a prognostic value in cancer as well as it may act as a mediator in cancer chemoresistance. Here, we aimed to investigate the underlying molecular mechanism of VAV3 in cancer progression as well as to review its value as a prognostic biomarker and chemoresistance mediator in human cancers. © 2023 Elsevier GmbH