Phenotypic switching and prostate diseases: a model proposing a causal link between benign prostatic hyperplasia and prostate cancer

Kulkarni, P and Nathan, A and Salgia, R and Rangarajan, G and Jolly, MK (2020) Phenotypic switching and prostate diseases: a model proposing a causal link between benign prostatic hyperplasia and prostate cancer. [Book Chapter]

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Abstract

A causal link between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) although suspected has thus far remained elusive. As far as we are aware, the integrated model proposed here is the first to establish this causality. The integrated model provides a conceptual basis to link plasticity at the molecular level conformational dynamics of the intrinsically disordered protein (IDPs) to phenotypic plasticity at the cellular level and provides a theoretical framework to illustrate how phenotypic plasticity of the impressionable prostate can give rise to both (symptomatic) BPH and PCa. The key aspects that eclipse symptomatic BPH and PCa including its precursors are stress, including inflammation and oxidative damage, upregulation of IDPs such as prostate-associated gene 4 (PAGE4) and the epithelial-to-mesenchymal transition markers OVOL1/2, ZEB1, and SNAI1, and the coexpression of PAGE4 and the AP-1 complex. Together these aspects that constitute the underpinnings of the integrated model provide compelling evidence linking this causality. Furthermore, the fact that the conformational ensembles of IDPs can be remodeled to populate different clusters that can promiscuously interact with different partners and hence, guide different functional outputs with large functional consequences such as state switching, underscores the virtues of the integrated model in demonstrating the causality. As additional evidence accumulates in the future, the integrated model will not only reaffirm the role of phenotypic switching in BPH and PCa but will also confirm the causal link between these two prostate diseases. Establishing this causality can improve the accuracy of disease prognostication and expedite intervention, perhaps even preemptively. © 2020 Elsevier Inc.

Item Type:	Book Chapter
Publication:	Phenotypic Switching: Implications in Biology and Medicine
Publisher:	Elsevier
Additional Information:	The copyright for this article belongs to Elsevier.
Keywords:	Benign prostatic hyperplasia; Phenotypic switching; Prostate cancer; Prostate peripheral zone; Prostate transition zone
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Physical & Mathematical Sciences > Mathematics
Date Deposited:	07 Feb 2023 04:05
Last Modified:	07 Feb 2023 04:05
URI:	https://eprints.iisc.ac.in/id/eprint/79965

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