Signaling mechanisms of Vav3, a guanine nucleotide exchange factor and androgen receptor coactivator, in physiology and prostate cancer progression

Leah S. Lyons, Kerry L Burnstein

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vav family of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPase activity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration- resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.

Original languageEnglish (US)
Title of host publicationProstate Cancer
Subtitle of host publicationBiochemistry, Molecular Biology and Genetics
PublisherSpringer New York
Pages187-205
Number of pages19
ISBN (Electronic)9781461468288
ISBN (Print)9781461468271
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

  • Medicine(all)

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