Mutant PIK3CA induces EMT in a cell type specific manner

Divya Bhagirath, Xiangshan Zhao, Sameer Mirza, William W. West, Hamid Band, Vimla Band

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Breast cancer is characterized into different molecular subtypes, and each subtype is characterized by differential gene expression that are associated with distinct survival outcomes in patients. PIK3CA mutations are commonly associated with most breast cancer subtypes. More recently PIK3CA mutations have been shown to induce tumor heterogeneity and are associated with activation of EGFR-signaling and reduced relapse free survival in basal subtype of breast cancer. Thus, understanding what determines PIK3CA induced heterogeneity and oncogenesis, is an important area of investigation. In this study, we assessed the effect of mutant PIK3CA together with mutant Ras plus mutant p53 on oncogenic behavior of two distinct stem/progenitor breast cell lines, designated as K5+/K19- and K5+/K19+. Constructs were ectopically overexpressed in K5+/K19- and K5+/K19+ stem/progenitor cells, followed by various in-vitro and in-vivo analyses. Oncogene combination m-Ras/m-p53/m-PIK3CA efficiently transformed both K5+/K19- and K5+/K19+ cell lines in-vitro, as assessed by anchorage-independent soft agar colony formation assay. Significantly, while this oncogene combination induced a complete epithelial-to-mesenchymal transition (EMT) in K5+/K19- cell line, mostly epithelial phenotype with minor EMT component was seen in K5+/K19+ cell line. However, both K5+/K19- and K5+/K19+ transformed cells exhibited increased invasion and migration abilities. Analyses of CD44 and CD24 expression showed both cell lines had tumor-initiating CD44+/CD24low cell population, however transformed K5+/K19- cells had more proportion of these cells. Significantly, both cell types exhibited in-vivo tumorigenesis, and maintained their EMT and epithelial nature in-vivo in mice tumors. Notably, while both cell types exhibited increase in tumor-initiating cell population, differential EMT phenotype was observed in these cell lines. These results suggest that EMT is a cell type dependent phenomenon and does not dictate oncogenesis.

Original languageEnglish (US)
Article numbere0167064
JournalPloS one
Volume11
Issue number12
DOIs
StatePublished - Dec 2016

Fingerprint

Epithelial-Mesenchymal Transition
Cells
cell lines
mutants
Cell Line
Tumors
breast neoplasms
carcinogenesis
cells
Carcinogenesis
Stem Cells
oncogenes
Breast Neoplasms
Oncogenes
neoplasms
stem cells
Phenotype
mutation
phenotype
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Mutant PIK3CA induces EMT in a cell type specific manner. / Bhagirath, Divya; Zhao, Xiangshan; Mirza, Sameer; West, William W.; Band, Hamid; Band, Vimla.

In: PloS one, Vol. 11, No. 12, e0167064, 12.2016.

Research output: Contribution to journalArticle

Bhagirath, Divya ; Zhao, Xiangshan ; Mirza, Sameer ; West, William W. ; Band, Hamid ; Band, Vimla. / Mutant PIK3CA induces EMT in a cell type specific manner. In: PloS one. 2016 ; Vol. 11, No. 12.
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