Academic Journal
Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer
| Title: | Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer |
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| Authors: | Hayato Ota, Hirokazu Sato, Shuji Mizumoto, Ken Wakai, Kei Yoneda, Kazuo Yamamoto, Hayao Nakanishi, Jun-Ichiro Ikeda, Shinichi Sakamoto, Tomohiko Ichikawa, Shuhei Yamada, Satoru Takahashi, Yuzuru Ikehara, Shoko Nishihara |
| Source: | Scientific Reports, Vol 13, Iss 1, Pp 1-16 (2023) |
| Publisher Information: | Nature Portfolio, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Medicine, Science |
| More Details: | Abstract Androgen deprivation therapy is given to suppress prostate cancer growth; however, some cells continue to grow hormone-independently as castration-resistant prostate cancer (CRPC). Sulfated glycosaminoglycans promote ligand binding to receptors as co-receptors, but their role in CRPC remains unknown. Using the human prostate cancer cell line C4-2, which can proliferate in hormone-dependent and hormone-independent conditions, we found that epidermal growth factor (EGF)-activated EGFR–ERK1/2 signaling via 3-O-sulfated heparan sulfate (HS) produced by HS 3-O-sulfotransferase 1 (HS3ST1) is activated in C4-2 cells under hormone depletion. Knockdown of HS3ST1 in C4-2 cells suppressed hormone-independent growth, and inhibited both EGF binding to the cell surface and activation of EGFR–ERK1/2 signaling. Gefitinib, an EGFR inhibitor, significantly suppressed C4-2 cell proliferation and growth of a xenografted C4-2 tumor in castrated mouse. Collectively, our study has revealed a mechanism by which cancer cells switch to hormone-independent growth and identified the key regulator as 3-O-sulfated HS. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-38746-x |
| Access URL: | https://doaj.org/article/aa8c11582cf6481ba26e4b14fd87cada |
| Accession Number: | edsdoj.8c11582cf6481ba26e4b14fd87cada |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-023-38746-x |
| Published in: | Scientific Reports |
| Language: | English |