@article{01240d32b2b94e72bb86c4edf91be746,
title = "Nerve growth factor interacts with CHRM4 and promotes neuroendocrine differentiation of prostate cancer and castration resistance",
abstract = "Nerve growth factor (NGF) contributes to the progression of malignancy. However, the functional role and regulatory mechanisms of NGF in the development of neuroendocrine prostate cancer (NEPC) are unclear. Here, we show that an androgen-deprivation therapy (ADT)-stimulated transcription factor, ZBTB46, upregulated NGF via ZBTB46 mediated-transcriptional activation of NGF. NGF regulates NEPC differentiation by physically interacting with a G-protein-coupled receptor, cholinergic receptor muscarinic 4 (CHRM4), after ADT. Pharmacologic NGF blockade and NGF knockdown markedly inhibited CHRM4-mediated NEPC differentiation and AKT-MYCN signaling activation. CHRM4 stimulation was associated with ADT resistance and was significantly correlated with increased NGF in high-grade and small-cell neuroendocrine prostate cancer (SCNC) patient samples. Our results reveal a role of the NGF in the development of NEPC that is linked to ZBTB46 upregulation and CHRM4 accumulation. Our study provides evidence that the NGF-CHRM4 axis has potential to be considered as a therapeutic target to impair NEPC progression.",
author = "Chen, {Wei Yu} and Wen, {Yu Ching} and Lin, {Shian Ren} and Yeh, {Hsiu Lien} and Jiang, {Kuo Ching} and Chen, {Wei Hao} and Lin, {Yow Sien} and Qingfu Zhang and Liew, {Phui Ly} and Michael Hsiao and Jiaoti Huang and Liu, {Yen Nien}",
note = "Funding Information: This work was jointly supported by grants from the Ministry of Science and Technology of Taiwan (MOST108-2320-B-038-047) to W.-Y.C. and (MOST108-2628-B-038-001 and MOST109-2326-B-038-001-MY3) to Y.-N.L., Taipei Medical University-Wan Fang Hospital (108TMU-WFH-03) to W.-Y.C., and the National Health Research Institute of Taiwan (NHRI-EX109-10702BI) to Y.-N.L. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2021",
month = dec,
doi = "10.1038/s42003-020-01549-1",
language = "English",
volume = "4",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}
