Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer

Gaurav A. Mehta, Joel S. Parker, Grace O. Silva, Katherine A. Hoadley, Charles M. Perou, Michael L. Gatza

Research output: Research - peer-reviewArticle

Abstract

Purpose: The PI3K/Akt signaling axis contributes to the dysregulation of many dominant features in breast cancer including cell proliferation, survival, metabolism, motility, and genomic instability. While multiple studies have demonstrated that basal-like or triple-negative breast tumors have uniformly high PI3K/Akt activity, genomic alterations that mediate dysregulation of this pathway in this subset of highly aggressive breast tumors remain to be determined. Methods: In this study, we present an integrated genomic analysis based on the use of a PI3K gene expression signature as a framework to analyze orthogonal genomic data from human breast tumors, including RNA expression, DNA copy number alterations, and protein expression. In combination with data from a genome-wide RNA-mediated interference screen in human breast cancer cell lines, we identified essential genetic drivers of PI3K/Akt signaling. Results: Our in silico analyses identified SOX4 amplification as a novel modulator of PI3K/Akt signaling in breast cancers and in vitro studies confirmed its role in regulating Akt phosphorylation. Conclusions: Taken together, these data establish a role for SOX4-mediated PI3K/Akt signaling in breast cancer and suggest that SOX4 may represent a novel therapeutic target and/or biomarker for current PI3K family therapies.

LanguageEnglish (US)
Pages439-450
Number of pages12
JournalBreast Cancer Research and Treatment
Volume162
Issue number3
DOIs
StatePublished - Apr 1 2017

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Phosphatidylinositol 3-Kinases
Breast Neoplasms
Family Therapy
Genomic Instability
RNA Interference
Transcriptome
Computer Simulation
Cell Survival
Biomarkers
Phosphorylation
Cell Proliferation
Genome
RNA
Cell Line
DNA
Proteins
Therapeutics
In Vitro Techniques

Keywords

  • Akt
  • Breast cancer
  • Genomics
  • PI3 kinase
  • SOX4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer. / Mehta, Gaurav A.; Parker, Joel S.; Silva, Grace O.; Hoadley, Katherine A.; Perou, Charles M.; Gatza, Michael L.

In: Breast Cancer Research and Treatment, Vol. 162, No. 3, 01.04.2017, p. 439-450.

Research output: Research - peer-reviewArticle

Mehta, Gaurav A. ; Parker, Joel S. ; Silva, Grace O. ; Hoadley, Katherine A. ; Perou, Charles M. ; Gatza, Michael L./ Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer. In: Breast Cancer Research and Treatment. 2017 ; Vol. 162, No. 3. pp. 439-450
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