STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization

• Kitai, Yuichi

• Iwakami, Masashi

• Saitoh, Kodai

• Togi, Sumihito

• Isayama, Serina

• Sekine, Yuichi

• Muromoto, Ryuta

• Kashiwakura, Jun-ichi

• Yoshimura, Akihiko

• Oritani, Kenji

• Matsuda, Tadashi

Abstract

Signal-transducing adaptor family member-2 (STAP-2) is an adaptor protein that regulates various intracellular signaling pathways and promotes tumorigenesis in melanoma and breast cancer cells. However, the contribution of STAP-2 to the behavior of other types of cancer cells is unclear. Here, we show that STAP-2 promotes tumorigenesis of prostate cancer cells through up-regulation of EGF receptor (EGFR) signaling. Tumor growth of a prostate cancer cell line, DU145, was strongly decreased by STAP-2 knockdown. EGF-induced gene expression and phosphorylation of AKT, ERK, and STAT3 were significantly decreased in STAP-2-knockdown DU145 cells. Mechanistically, we found that STAP-2 interacted with EGFR and enhanced its stability by inhibiting c-CBL-mediated EGFR ubiquitination. Our results indicate that STAP-2 promotes prostate cancer progression via facilitating EGFR activation.

Journal

• Journal of Biological Chemistry (JBC)

  Journal of Biological Chemistry (JBC) 292 (47), 19392-19399, 2017-11-24

  American Society for Biochemistry and Molecular Biology (ASBMB)

Keywords

• adaptor protein
• prostate cancer
• protein degradation
• signal transduction
• STAT3
• c-CBL

Details

• CRID: 1050845763984831488
• NII Article ID: 120006539248
• DOI: 10.1074/jbc.m117.802884
• HANDLE: 2115/72029
• ISSN: 00219258
• Web Site: https://api.elsevier.com/content/article/PII:S0021925820329070?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021925820329070?httpAccept=text/plain
• Web Site: https://syndication.highwire.org/content/doi/10.1074/jbc.M117.802884
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN