Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene

Research output: Contribution to journalArticle

Abstract

Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. In this report, how WASF3 overexpression interacts with mutant RAS to increase invasion and metastasis was investigated. The ability of RAS to promote invasion and metastasis was shown to be dependent on WASF3 activation in a PI3K and AKT dependent manner. Proteomics analysis demonstrates the presence of AKT in the WASF3 immunocomplex which is enhanced by overexpression of mutant RAS. During these processes activation of ERK1/2 is not affected by loss of WASF3 expression. Analysis of the relative involvement of p85 and p110 in the WASF3 complex demonstrates that mutant RAS promotes dissociation of p85 promoting activation of p110. These studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalGenes Chromosomes and Cancer
Volume56
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Neoplasm Metastasis
Genes
Wiskott-Aldrich Syndrome Protein Family
Actin Cytoskeleton
Phosphatidylinositol 3-Kinases
Proteomics
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene. / Teng, Yong; Ngoka, Lambert; Cowell, John Kenneth.

In: Genes Chromosomes and Cancer, Vol. 56, No. 6, 01.06.2017, p. 493-500.

Research output: Contribution to journalArticle

@article{c11811deacd04ab2ba167dd7f99346e9,
title = "Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene",
abstract = "Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. In this report, how WASF3 overexpression interacts with mutant RAS to increase invasion and metastasis was investigated. The ability of RAS to promote invasion and metastasis was shown to be dependent on WASF3 activation in a PI3K and AKT dependent manner. Proteomics analysis demonstrates the presence of AKT in the WASF3 immunocomplex which is enhanced by overexpression of mutant RAS. During these processes activation of ERK1/2 is not affected by loss of WASF3 expression. Analysis of the relative involvement of p85 and p110 in the WASF3 complex demonstrates that mutant RAS promotes dissociation of p85 promoting activation of p110. These studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis.",
author = "Yong Teng and Lambert Ngoka and Cowell, {John Kenneth}",
year = "2017",
month = "6",
day = "1",
doi = "10.1002/gcc.22453",
language = "English (US)",
volume = "56",
pages = "493--500",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Promotion of invasion by mutant RAS is dependent on activation of the WASF3 metastasis promoter gene

AU - Teng, Yong

AU - Ngoka, Lambert

AU - Cowell, John Kenneth

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. In this report, how WASF3 overexpression interacts with mutant RAS to increase invasion and metastasis was investigated. The ability of RAS to promote invasion and metastasis was shown to be dependent on WASF3 activation in a PI3K and AKT dependent manner. Proteomics analysis demonstrates the presence of AKT in the WASF3 immunocomplex which is enhanced by overexpression of mutant RAS. During these processes activation of ERK1/2 is not affected by loss of WASF3 expression. Analysis of the relative involvement of p85 and p110 in the WASF3 complex demonstrates that mutant RAS promotes dissociation of p85 promoting activation of p110. These studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis.

AB - Metastasis represents an end stage in the evolution of cancer progression and has been related to specific genetic pathways. Overexpression of mutant RAS in particular appears to promote invasion and metastasis, although exactly how this occurs has not been well characterized. It was previously showed that activation of the WASF3 protein regulates actin cytoskeleton dynamics that promote invasion. In this report, how WASF3 overexpression interacts with mutant RAS to increase invasion and metastasis was investigated. The ability of RAS to promote invasion and metastasis was shown to be dependent on WASF3 activation in a PI3K and AKT dependent manner. Proteomics analysis demonstrates the presence of AKT in the WASF3 immunocomplex which is enhanced by overexpression of mutant RAS. During these processes activation of ERK1/2 is not affected by loss of WASF3 expression. Analysis of the relative involvement of p85 and p110 in the WASF3 complex demonstrates that mutant RAS promotes dissociation of p85 promoting activation of p110. These studies provide a deeper understanding of the critical role for WASF3 in facilitating increased invasion potential in cancer cells expressing mutant RAS and supports the idea that targeting WASF3 in metastatic cells overexpressing RAS may be used to suppress invasion and metastasis.

UR - http://www.scopus.com/inward/record.url?scp=85017384117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017384117&partnerID=8YFLogxK

U2 - 10.1002/gcc.22453

DO - 10.1002/gcc.22453

M3 - Article

VL - 56

SP - 493

EP - 500

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 6

ER -