VAV3 in human cancers: Mechanism and clinical implication

Sulieman Ibraheem Shelash Al-Hawary; Ali Alsalamy; Reena Gupta; Hashem O Alsaab; Ahmed Hjazi; Unarbek Edilboyev; Montather F Ramadan; Beneen M Hussien; Muhja Ahmed; Seyed Reza Hosseini-Fard

doi:10.1016/j.prp.2023.154681

VAV3 in human cancers: Mechanism and clinical implication

Pathol Res Pract. 2023 Aug:248:154681. doi: 10.1016/j.prp.2023.154681. Epub 2023 Jul 13.

Affiliations

¹ Departemnt of Business Administration, Business School, Al-Bayt University, P.O.BOX 130040, Mafraq 25113, Jordan.
² College of Engineering, Imam Ja'afar Al-Sadiq University, Al-Muthanna 66002, Iraq.
³ Institute of Pharmaceutical Research, GLA University, District-Mathura, U.P., 281406, India.
⁴ Department of Pharmaceutics and Pharmaceutical Technology, Taif University, Taif 21944, Saudi Arabia.
⁵ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁶ Department of Engineering Graphics and Design Theory, Tashkent Institute of Irrigation and Agricultural Mechanization Engineers, National Research University, Tashkent, Uzbekistan.
⁷ College of Dentistry, Al-Ayen University, Thi-Qar, Iraq ‏.
⁸ Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq.
⁹ Medical Technical College, Al-Farahidi University, Baghdad, Iraq.
¹⁰ Biochemistry Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Rhoseinifard@razi.tums.ac.ir.

PMID: 37467637
DOI: 10.1016/j.prp.2023.154681

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.

Keywords: Biomarker; Cancer; GEF; VAV3.

Publication types

Review

MeSH terms

Humans
Neoplasms*
Phosphorylation
Proto-Oncogene Proteins c-vav* / metabolism
Receptors, Cell Surface / metabolism
Signal Transduction

Substances

Proto-Oncogene Proteins c-vav
Receptors, Cell Surface
VAV3 protein, human