OVOL guides the epithelial-hybrid-mesenchymal transition

Dongya Jia, Mohit Kumar Jolly, Marcelo Boareto, Princy Parsana, Steven M. Mooney, Kenneth J. Pienta, Herbert Levine, Eshel Ben-Jacob

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis involves multiple cycles of Epithelial-to-Mesenchymal Transition (EMT) and its reverse-MET. Cells can also undergo partial transitions to attain a hybrid epithelial/mesenchymal (E/M) phenotype that has maximum cellular plasticity and allows migration of Circulating Tumor Cells (CTCs) as a cluster. Hence, deciphering the molecular players helping to maintain the hybrid E/M phenotype may inform antimetastasis strategies. Here, we devised a mechanism-based mathematical model to couple the transcription factor OVOL with the core EMT regulatory network miR-200/ ZEB that acts as a three-way switch between the E, E/M and M phenotypes. We show that OVOL can modulate cellular plasticity in multiple ways - restricting EMT, driving MET, expanding the existence of the hybrid E/M phenotype and turning both EMT and MET into two-step processes. Our theoretical framework explains the differences between the observed effects of OVOL in breast and prostate cancer, and provides a platform for investigating additional signals during metastasis.

Original languageEnglish (US)
Pages (from-to)15436-15448
Number of pages13
JournalOncotarget
Volume6
Issue number17
DOIs
StatePublished - 2015

Keywords

  • Cancer systems biology
  • EMT
  • Metastasis
  • OVOL
  • Partial EMT

ASJC Scopus subject areas

  • Oncology

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