| Full text | |
| Author(s): |
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]
Total Authors: 8
|
| Affiliation: Show less - | [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
Total Affiliations: 13
|
| Document type: | Journal article |
| Source: | ONCOTARGET; v. 6, n. 17, p. 15436-15448, JUN 20 2015. |
| Web of Science Citations: | 41 |
| 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 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) | |
| FAPESP's process: | 13/14438-8 - Study of gene regulatory network by stochastic methods and statistical mechanics |
| Grantee: | Marcelo Boareto Do Amaral |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate (Direct) |