Singh, D and Bocci, F and Kulkarni, P and Jolly, MK (2021) Coupled feedback loops involving PAGE4, EMT and notch signaling can give rise to non-genetic heterogeneity in prostate cancer cells. In: Entropy, 23 (3). pp. 1-16.
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Abstract
Non-genetic heterogeneity is emerging as a crucial factor underlying therapy resistance in multiple cancers. However, the design principles of regulatory networks underlying non-genetic heterogeneity in cancer remain poorly understood. Here, we investigate the coupled dynamics of feedback loops involving (a) oscillations in androgen receptor (AR) signaling mediated through an intrinsically disordered protein PAGE4, (b) multistability in epithelial-mesenchymal transition (EMT), and c) Notch-Delta-Jagged signaling mediated cell-cell communication, each of which can generate non-genetic heterogeneity through multistability and/or oscillations. Our results show how different coupling strengths between AR and EMT signaling can lead to monostability, bistability, or oscillations in the levels of AR, as well as propagation of oscillations to EMT dynamics. These results reveal the emergent dynamics of coupled oscillatory and multi-stable systems and unravel mechanisms by which non-genetic heterogeneity in AR levels can be generated, which can act as a barrier to most existing therapies for prostate cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
| Item Type: | Journal Article |
|---|---|
| Publication: | Entropy |
| Publisher: | MDPI AG |
| Additional Information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering UG Programme |
| Date Deposited: | 30 Mar 2021 12:01 |
| Last Modified: | 31 Mar 2021 07:23 |
| URI: | http://eprints.iisc.ac.in/id/eprint/68516 |
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