@article{33f0b327f94949fe9d44e44392d1f374,
title = "OCT1-target neural gene PFN2 promotes tumor growth in androgen receptor-negative prostate cancer",
abstract = "Androgen and androgen receptor (AR) targeted therapies are the main treatment for most prostate cancer (PC) patients. Although AR signaling inhibitors are effective, tumors can evade this treatment by transforming to an AR-negative PC via lineage plasticity. OCT1 is a transcription factor interacting with the AR to enhance signaling pathways involved in PC progression, but its role in the emergence of the AR-negative PC is unknown. We performed chromatin immunoprecipitation sequencing (ChIP-seq) in patient-derived castration-resistant AR-negative PC cells to identify genes that are regulated by OCT1. Interestingly, a group of genes associated with neural precursor cell proliferation was significantly enriched. Then, we focused on neural genes STNB1 and PFN2 as OCT1-targets among them. Immunohistochemistry revealed that both STNB1 and PFN2 are highly expressed in human AR-negative PC tissues. Knockdown of SNTB1 and PFN2 by siRNAs significantly inhibited migration of AR-negative PC cells. Notably, knockdown of PFN2 showed a marked inhibitory effect on tumor growth in vivo. Thus, we identified OCT1-target genes in AR-negative PC using a patient-derived model, clinicopathologial analysis and an animal model.",
author = "Daisuke Obinata and Daigo Funakoshi and Kenichi Takayama and Makoto Hara and Birunthi Niranjan and Linda Teng and Lawrence, {Mitchell G.} and Taylor, {Renea A.} and Risbridger, {Gail P.} and Yutaka Suzuki and Satoru Takahashi and Satoshi Inoue",
note = "Funding Information: We acknowledge the patient representatives, clinical co-ordinators, scientists, and clinicians, who contribute to the Melbourne Urological Research Alliance (MURAL) and its collection of patient-derived models; the CASCADE rapid autopsy program at the Peter MacCallum Cancer Centre, including Shahneen Sandhu, Lisa Devereux, and Heather Thorne for providing patient tissue; the Monash Biomedicine Discovery Institute Organoid Program for reagents; and technical assistance from Hong Wang, Melissa Papargiris, Jenna Kraska, Asako Oguni, Toyoharu Jike, Isamu Isahai, and Naoko Abe. The authors are supported by funding from the National Health and Medical Research Council, Australia (fellowship to G.P.R. 1102752, project Grants 1138242), the Department of Health and Human Services acting through the Victorian Cancer Agency (fellowship to M.G.L. MCRF18017, fellowship to R.A.T MCRF15023), P-CREATE (Grant number JP18ck0106194 from AMED, Japan to SI), Takeda Science Foundation, and JSPS KAKENHI (Grant numbers JP19H03793 to DO, JP19K09740 to ST, and JP20K07875 to MH, JP20K21667 and JP21H04829 to SI). Funding Information: We acknowledge the patient representatives, clinical co-ordinators, scientists, and clinicians, who contribute to the Melbourne Urological Research Alliance (MURAL) and its collection of patient-derived models; the CASCADE rapid autopsy program at the Peter MacCallum Cancer Centre, including Shahneen Sandhu, Lisa Devereux, and Heather Thorne for providing patient tissue; the Monash Biomedicine Discovery Institute Organoid Program for reagents; and technical assistance from Hong Wang, Melissa Papargiris, Jenna Kraska, Asako Oguni, Toyoharu Jike, Isamu Isahai, and Naoko Abe. The authors are supported by funding from the National Health and Medical Research Council, Australia (fellowship to G.P.R. 1102752, project Grants 1138242), the Department of Health and Human Services acting through the Victorian Cancer Agency (fellowship to M.G.L. MCRF18017, fellowship to R.A.T MCRF15023), P-CREATE (Grant number JP18ck0106194 from AMED, Japan to SI), Takeda Science Foundation, and JSPS KAKENHI (Grant numbers JP19H03793 to DO, JP19K09740 to ST, and JP20K07875 to MH, JP20K21667 and JP21H04829 to SI). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41598-022-10099-x",
language = "English",
volume = "12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}