MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer

Yota Yasumizu, Hasan Rajabi, Caining Jin, Tsuyoshi Hata, Sean Pitroda, Mark D. Long, Masayuki Hagiwara, Wei Li, Qiang Hu, Song Liu, Nami Yamashita, Atsushi Fushimi, Ling Kui, Mehmet Samur, Masaaki Yamamoto, Yan Zhang, Ning Zhang, Deli Hong, Takahiro Maeda, Takeo Kosaka, Kwok K. Wong, Mototsugu Oya and Donald Kufe ()
Additional contact information
Yota Yasumizu: Dana-Farber Cancer Institute Harvard Medical School
Hasan Rajabi: Dana-Farber Cancer Institute Harvard Medical School
Caining Jin: Dana-Farber Cancer Institute Harvard Medical School
Tsuyoshi Hata: Dana-Farber Cancer Institute Harvard Medical School
Sean Pitroda: University of Chicago
Mark D. Long: Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center
Masayuki Hagiwara: Dana-Farber Cancer Institute Harvard Medical School
Wei Li: Dana-Farber Cancer Institute Harvard Medical School
Qiang Hu: Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center
Song Liu: Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center
Nami Yamashita: Dana-Farber Cancer Institute Harvard Medical School
Atsushi Fushimi: Dana-Farber Cancer Institute Harvard Medical School
Ling Kui: Dana-Farber Cancer Institute Harvard Medical School
Mehmet Samur: Dana-Farber Cancer Institute Harvard Medical School
Masaaki Yamamoto: Dana-Farber Cancer Institute Harvard Medical School
Yan Zhang: Dana-Farber Cancer Institute Harvard Medical School
Ning Zhang: Dana-Farber Cancer Institute Harvard Medical School
Deli Hong: Dana-Farber Cancer Institute Harvard Medical School
Takahiro Maeda: Keio University School of Medicine Shinjuku-ku
Takeo Kosaka: Keio University School of Medicine Shinjuku-ku
Kwok K. Wong: New York University Langone Medical Center
Mototsugu Oya: Keio University School of Medicine Shinjuku-ku
Donald Kufe: Dana-Farber Cancer Institute Harvard Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Neuroendocrine prostate cancer (NEPC) is an aggressive malignancy with no effective targeted therapies. The oncogenic MUC1-C protein is overexpressed in castration-resistant prostate cancer (CRPC) and NEPC, but its specific role is unknown. Here, we demonstrate that upregulation of MUC1-C in androgen-dependent PC cells suppresses androgen receptor (AR) axis signaling and induces the neural BRN2 transcription factor. MUC1-C activates a MYC→BRN2 pathway in association with induction of MYCN, EZH2 and NE differentiation markers (ASCL1, AURKA and SYP) linked to NEPC progression. Moreover, MUC1-C suppresses the p53 pathway, induces the Yamanaka pluripotency factors (OCT4, SOX2, KLF4 and MYC) and drives stemness. Targeting MUC1-C decreases PC self-renewal capacity and tumorigenicity, suggesting a potential therapeutic approach for CRPC and NEPC. In PC tissues, MUC1 expression associates with suppression of AR signaling and increases in BRN2 expression and NEPC score. These results highlight MUC1-C as a master effector of lineage plasticity driving progression to NEPC.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-14219-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14219-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-14219-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().