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Phenotypic plasticity and lineage switching in prostate cancer

Somarelli, JA and Armstrong, AJ and Sheth, MU and Ware, KE and Jolly, MK (2020) Phenotypic plasticity and lineage switching in prostate cancer. [Book Chapter]

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Official URL: https://doi.org/10.1016/B978-0-12-817996-3.00021-9


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.

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: Androgen receptor; Enzalutamide; Epithelial-mesenchymal transition; Lineage plasticity; Neuroendocrine prostate cancer; Phenotypic plasticity
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 07 Feb 2023 03:56
Last Modified: 07 Feb 2023 03:56
URI: https://eprints.iisc.ac.in/id/eprint/79961

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