Embigin promotes prostate cancer progression by S100A4-dependent and-independent mechanisms

I. Made Winarsa Ruma, Rie Kinoshita, Nahoko Tomonobu, Yusuke Inoue, Eisaku Kondo, Akira Yamauchi, Hiroki Sato, I. Wayan Sumardika, Youyi Chen, Ken Ichi Yamamoto, Hitoshi Murata, Shinichi Toyooka, Masahiro Nishibori, Masakiyo Sakaguchi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid-and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.

Original languageEnglish
Article number239
JournalCancers
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 23 2018

Keywords

  • AMPK
  • Embigin
  • Extracellular S100A4
  • Prostate cancer progression
  • mTORC1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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