Interaction between SCP3 and JAB1 confers cancer therapeutic resistance and stem-like properties through EGF expression

Se Jin Oh, Kyung Hee Noh, Kwon Ho Song, Tae Woo Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, has been implicated in cancer progression, and therapeutic resistance, as well as cancer stem cell (CSC)-like properties. Previously, we demonstrated that SCP3 promotes these aggressive phenotypes via hyperactivation of the AKT signaling pathway; however, the underlying mechanisms responsible for SCP3-induced AKT activation remain to be elucidated. In this study, we demonstrated that the EGF-EGFR axis is the primary route through which SCP3 acts to activate AKT signaling. SCP3 triggers the EGFR-AKT pathway through transcriptional activation of EGF. Notably, neutralization of secreted EGF by its specific monoclonal antibody reversed SCP3-mediated aggressive phenotypes with a concomitant reversal of EGFR-AKT activation. In an effort to elucidate the molecular mechanisms underlying SCP3-induced transcriptional activation of EGF, we identified Jun activation domain-binding protein 1 (JAB1) as a binding partner of SCP3 using a yeast two-hybrid (Y2H) assay system, and we demonstrated that SCP3 induces EGF transcription through physical interaction with JAB1. Thus, our findings establish a firm molecular link among SCP3, EGFR, and AKT by identifying the novel roles of SCP3 in transcriptional regulation. We believe that these findings hold important implications for controlling SCP3high therapeutic-refractory cancer.

Original languageEnglish
Article number8839
JournalInternational journal of molecular sciences
Volume22
Issue number16
DOIs
Publication statusPublished - 2021 Aug 2

Keywords

  • AKT
  • Cancer
  • Cancer stem cell (CSC)
  • Chemo-resistance
  • Epidermal growth factor (EGF)
  • Epidermal growth factor receptor (EGFR)
  • Immune resistance
  • Jun activation domain-binding protein 1 (JAB1)
  • Synaptonemal complex protein 3 (SCP3)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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