OVOL guides the epithelial-hybrid-mesenchymal transition

Autor(es)

Jia, Dongya ^{[1, 2]} ; Jolly, Mohit Kumar ^{[1, 3]} ; Boareto, Marcelo ^{[4, 1]} ; Parsana, Princy ^[5] ; Mooney, Steven M. ^{[6, 7]} ; Pienta, Kenneth J. ^{[6, 7, 8, 9]} ; Levine, Herbert ^{[1, 3, 10]} ; Ben-Jacob, Eshel ^{[1, 11, 12, 13]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA

^[2] Rice Univ, Grad Program Syst Synthet & Phys Biol, Houston, TX 77005 - USA

^[3] Rice Univ, Dept Bioengn, Houston, TX 77005 - USA

^[4] Univ Sao Paulo, Inst Phys, BR-05508 Sao Paulo - Brazil

^[5] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21287 - USA

^[6] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Sch Med, Baltimore, MD 21287 - USA

^[7] Johns Hopkins Univ, Dept Urol, Sch Med, Baltimore, MD 21287 - USA

^[8] Johns Hopkins Univ, Dept Oncol, Sch Med, Baltimore, MD 21287 - USA

^[9] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21287 - USA

^[10] Rice Univ, Dept Phys & Astron, Houston, TX 77005 - USA

^[11] Rice Univ, Dept Biosci, Houston, TX 77005 - USA

^[12] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv - Israel

^[13] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv - Israel

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 6, n. 17, p. 15436-15448, JUN 20 2015.
• Citações Web of Science: 41

Resumo

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 anti-metastasis 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. (AU)

• Processo FAPESP: 13/14438-8 - Estudo de redes gênicas regulatórias por meio de métodos estocásticos e de mecânica estatística
• Beneficiário: Marcelo Boareto Do Amaral
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto