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. 2021 Jul 9;13(14):3452. doi: 10.3390/cancers13143452

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Interplay between the epidermal growth factor receptor (EGFR) and signal transduction and activator of transcription 3 (STAT3) in castration-resistant prostate cancer (CRPC) and CRPC-neuroendocrine (NE) development. Androgen deprivation therapy (ADT) stimulates EGFR translocation, followed by the leukemia-inhibitory factor receptor (LIFR) expression. The LIFR activates STAT3 and promotes SUCLG2 expression, which triggers neuroendocrine differentiation (NED). A black solid arrow represents signal transduction; a black dashed arrow represents translocation of proteins; a black faded arrow represents peptide hormones that bind to receptors; a red arrow shows the cell fate.