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bioRxiv · 10.1101/2025.11.10.687642

NEUROG3 Is Sufficient to Drive Neuroendocrine Differentiation in Prostate Cancer Cells.

Daoud, A.·Han, L.·Christensen, R. K.·Munera, J. O.
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Abstract

Treatment-emergent neuroendocrine prostate cancer (t-NEPC) arises following androgen deprivation therapy, leading to androgen-independent growth. Although multiple factors have been shown to be necessary for neuroendocrine differentiation (NED), their sufficiency has not been demonstrated. The prostate and colorectum share a common hindgut origin, and prostate neuroendocrine cell markers overlap with colorectal enteroendocrine cell (EEC) markers. Analysis of patient datasets revealed NEUROG3 amplification in both castration-resistant and neuroendocrine prostate cancers, correlating with poor survival. Because Neurogenin-3 (NEUROG3) is necessary and sufficient for EEC differentiation in the colorectum, we hypothesized that it could similarly drive NED in prostate cancer cells. A transient pulse of NEUROG3 repressed luminal identity and activated neuroendocrine programs, producing neuroendocrine cells within seven days. In summary, our findings identify NEUROG3 as a potential mediator of prostate cancer progression and establish a rapid in vitro model in which its transient activation is sufficient to initiate neuroendocrine differentiation.

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Daoud, A., Han, L., Christensen, R. K., Munera, J. O.. 2025-11-12. NEUROG3 Is Sufficient to Drive Neuroendocrine Differentiation in Prostate Cancer Cells.. https://doi.org/10.1101/2025.11.10.687642

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