TY - JOUR
T1 - Phenotypic plasticity in prostate cancer
T2 - Role of intrinsically disordered proteins
AU - Mooney, Steven
AU - Jolly, Mohit
AU - Levine, Herbert
AU - Kulkarni, Prakash
N1 - Publisher Copyright:
© 2016 AJA, SIMM & SJTU.
PY - 2016/9
Y1 - 2016/9
N2 - A striking characteristic of cancer cells is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition (EMT) that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks (PINs) may play a key role in determining phenotypic plasticity in prostate cancer (PCA). Specifically, we point out that the key players driving transitions among different phenotypes (epithelial, mesenchymal, and hybrid epithelial/mesenchymal), including ZEB1, SNAI1, OVOL1, and OVOL2, are intrinsically disordered proteins (IDPs) and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting IDPs implicated in EMT in PCA may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men.
AB - A striking characteristic of cancer cells is their remarkable phenotypic plasticity, which is the ability to switch states or phenotypes in response to environmental fluctuations. Phenotypic changes such as a partial or complete epithelial to mesenchymal transition (EMT) that play important roles in their survival and proliferation, and development of resistance to therapeutic treatments, are widely believed to arise due to somatic mutations in the genome. However, there is a growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence, which indicate that stochasticity may also play an important role in driving phenotypic plasticity. Here, we discuss how stochasticity in protein interaction networks (PINs) may play a key role in determining phenotypic plasticity in prostate cancer (PCA). Specifically, we point out that the key players driving transitions among different phenotypes (epithelial, mesenchymal, and hybrid epithelial/mesenchymal), including ZEB1, SNAI1, OVOL1, and OVOL2, are intrinsically disordered proteins (IDPs) and discuss how plasticity at the molecular level may contribute to stochasticity in phenotypic switching by rewiring PINs. We conclude by suggesting that targeting IDPs implicated in EMT in PCA may be a new strategy to gain additional insights and develop novel treatments for this disease, which is the most common form of cancer in adult men.
KW - epithelial to mesenchymal transition
KW - intrinsically disordered proteins
KW - prostate cancer
KW - state-switching
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U2 - 10.4103/1008-682X.183570
DO - 10.4103/1008-682X.183570
M3 - Review article
C2 - 27427552
AN - SCOPUS:84983805983
SN - 1008-682X
VL - 18
SP - 704
EP - 710
JO - Asian Journal of Andrology
JF - Asian Journal of Andrology
IS - 5
ER -