Corrigendum
Open Access | 
10.1172/jci.insight.196861
ASCL1 regulates and cooperates with FOXA2 to drive terminal neuroendocrine phenotype in prostate cancer
Shaghayegh Nouruzi, Takeshi Namekawa, Nakisa Tabrizian, Maxim Kobelev, Olena Sivak, Joshua M Scurll, Cassandra Jingjing Cui, Dwaipayan Ganguli, and Amina Zoubeidi
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Published August 8, 2025 - More info
JCI Insight. 2025;10(15):e196861. https://doi.org/10.1172/jci.insight.196861.
© 2025 Nouruzi et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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Abstract
Lineage plasticity mediates resistance to androgen receptor pathway inhibitors (ARPIs) and progression from adenocarcinoma to neuroendocrine prostate cancer (NEPC), a highly aggressive and poorly understood subtype. Neuronal transcription factor ASCL1 has emerged as a central regulator of the lineage plasticity driving neuroendocrine differentiation. Here, we showed that ASCL1 was reprogrammed in ARPI-induced transition to terminal NEPC and identified that the ASCL1 binding pattern tailored the expression of lineage-determinant transcription factor combinations that underlie discrete terminal NEPC identity. Notably, we identified FOXA2 as a major cofactor of ASCL1 in terminal NEPC, which is highly expressed in ASCL1-driven NEPC. Mechanistically, FOXA2 and ASCL1 interacted and worked in concert to orchestrate terminal neuronal differentiation. We identified that prospero homeobox 1 was a target of ASCL1 and FOXA2. Targeting prospero homeobox 1 abrogated neuroendocrine characteristics and led to a decrease in cell proliferation in vitro and tumor growth in vivo. Our findings provide insights into the molecular conduit underlying the interplay between different lineage-determinant transcription factors to support the neuroendocrine identity and nominate prospero homeobox 1 as a potential target in ASCL1-high NEPC.
Authors
Shaghayegh Nouruzi, Takeshi Namekawa, Nakisa Tabrizian, Maxim Kobelev, Olena Sivak, Joshua M Scurll, Cassandra Jingjing Cui, Dwaipayan Ganguli, Amina Zoubeidi
Original citation: JCI Insight. 2024;9(23):e185952. https://doi.org/10.1172/jci.insight.185952
Citation for this corrigendum: JCI Insight. 2025;10(15):e196861. https://doi.org/10.1172/jci.insight.196861
The Methods have been updated to indicate the source of the tissue microarray data. The added text is below.
Tissue microarray. The tissue microarray was generated in 2016 by the pathology core at the Vancouver Prostate Centre (VPC), using British Columbian Canadian prostate cancer specimens obtained from surgeries performed at Vancouver General Hospital and UBC Hospital.
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