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Phenotypic Switching: Implications in Biology and Medicine

Phenotypic plasticity and lineage switching in prostate cancer

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Somarelli, JA; Armstrong, AJ; Sheth, MU; Ware, KE; Jolly, MK
January 1, 2020

In the United States alone prostate cancer is responsible for nearly 70 days each day. The vast majority of these deaths are due to metastatic spread of therapy-resistant disease. Metastasis and therapy resistance are mediated by phenotypic plasticity in which prostate cancer cells alter their cellular lineages from epithelial-like cells that are dependent on androgen receptor signaling to mesenchymal-like or neuroendocrine-like cells that are independent of androgen receptor signaling. This phenoptyic plasticity also promotes migratory, invasive, and chemoresistant properties. All of these properties are regulated by a series of secreted signaling molecules and intracellular transcription factors normally involved in lineage programming during development; however, during prostate cancer progression, these factors are reactivated, which induces lineage reprogramming and promotes metastasis and hormone therapy resistance. Interestingly, many of these factors are found in common during both epithelial-mesenchymal and neuroendocrine reprogramming; however, the exact relationships between the epithelial, mesenchymal, and neuroendocrine phenotypes remain poorly understood. Here we discuss the current understanding of the relationships between these overlapping, but distinct phenotypic transitions and highlight key unanswered questions about the mechanistic interconnections between epithelial-mesenchymal transition and neuroendocrine prostate cancer biology.

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January 1, 2020

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591 / 615
 

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Somarelli, J. A., Armstrong, A. J., Sheth, M. U., Ware, K. E., & Jolly, M. K. (2020). Phenotypic plasticity and lineage switching in prostate cancer. In Phenotypic Switching: Implications in Biology and Medicine (pp. 591–615). https://doi.org/10.1016/B978-0-12-817996-3.00021-9
Somarelli, J. A., A. J. Armstrong, M. U. Sheth, K. E. Ware, and M. K. Jolly. “Phenotypic plasticity and lineage switching in prostate cancer.” In Phenotypic Switching: Implications in Biology and Medicine, 591–615, 2020. https://doi.org/10.1016/B978-0-12-817996-3.00021-9.
Somarelli JA, Armstrong AJ, Sheth MU, Ware KE, Jolly MK. Phenotypic plasticity and lineage switching in prostate cancer. In: Phenotypic Switching: Implications in Biology and Medicine. 2020. p. 591–615.
Somarelli, J. A., et al. “Phenotypic plasticity and lineage switching in prostate cancer.” Phenotypic Switching: Implications in Biology and Medicine, 2020, pp. 591–615. Scopus, doi:10.1016/B978-0-12-817996-3.00021-9.
Somarelli JA, Armstrong AJ, Sheth MU, Ware KE, Jolly MK. Phenotypic plasticity and lineage switching in prostate cancer. Phenotypic Switching: Implications in Biology and Medicine. 2020. p. 591–615.

DOI

Publication Date

January 1, 2020

Start / End Page

591 / 615