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Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer

Chauhan, L and Ram, U and Hari, K and Jolly, MK (2021) Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer. In: eLife, 10 .

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Official URL: https://doi.org/10.7554/eLife.64522


Phenotypic (non-genetic) heterogeneity has significant implications for the development and evolution of organs, organisms, and populations. Recent observations in multiple cancers have unraveled the role of phenotypic heterogeneity in driving metastasis and therapy recalcitrance. However, the origins of such phenotypic heterogeneity are poorly understood in most cancers. Here, we investigate a regulatory network underlying phenotypic heterogeneity in small cell lung cancer, a devastating disease with no molecular targeted therapy. Discrete and continuous dynamical simulations of this network reveal its multistable behavior that can explain co-existence of four experimentally observed phenotypes. Analysis of the network topology uncovers that multistability emerges from two teams of players that mutually inhibit each other, but members of a team activate one another, forming a �toggle switch� between the two teams. Deciphering these topological signatures in cancer-related regulatory networks can unravel their �latent� design principles and offer a rational approach to characterize phenotypic heterogeneity in a tumor. © Chauhan et al.

Item Type: Journal Article
Publication: eLife
Publisher: eLife Sciences Publications Ltd
Additional Information: The copyright for this article belongs to the authors.
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 09 Jul 2021 06:02
Last Modified: 09 Jul 2021 06:02
URI: http://eprints.iisc.ac.in/id/eprint/68723

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