Disorder, Promiscuous Interactions, and Stochasticity Regulate State Switching in the Unstable Prostate

Prakash Kulkarni, Robert H. Getzenberg

Research output: Contribution to journalArticlepeer-review

Abstract

A causal link between benign prostatic hyperplasia (BPH) and prostate cancer has long been suspected but not widely accepted. A new model is proposed that supports such a connection. In contrast to the prevailing wisdom, our model, that draws on dynamical systems theory, suggests that in response to stress, epithelial cells in the unstable gland can give rise to both types of diseases via a phenotypic switching mechanism. The central idea is that phenotypic switching is a stochastic process which exploits the plasticity of the epithelial cell. It is driven by ‘noise’ contributed by the conformational dynamics of proteins that are intrinsically disordered. In a system that is noisy when stressed, disorder promotes promiscuity, unmasks latent information, and rewires the network to cause phenotypic switching. Cells with newly acquired phenotypes can transcend the traditional zonal boundaries to give rise to BPH or prostate cancer depending on the microenvironment. Establishing causality between the two diseases may provide us with an opportunity to better understand their etiology and guide prevention and treatment strategies. J. Cell. Biochem. 117: 2235–2240, 2016.

Original languageEnglish (US)
Pages (from-to)2235-2240
Number of pages6
JournalJournal of Cellular Biochemistry
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Keywords

  • BENIGN PROSTATIC HYPERPLASIA
  • CANCER/TESTIS ANTIGENS
  • PROSTATE CANCER
  • STATE SWITCHING

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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