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STAT3 mediates RCP-induced cancer cell invasion through the NF-κB/Slug/MT1-MMP signaling cascade

Su Jin Cho1, Bo Young Jeong1,2, Young Soo Song3

  • 1Department of Pharmacology, College of Medicine, Konyang University, 821 Medical Science Building, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea.

Archives of Pharmacal Research
|July 9, 2022
PubMed

Insights

Rab coupling protein (RCP) drives cancer invasion by activating STAT3 signaling. Inhibiting STAT3 blocks RCP-induced metastasis, revealing a key pathway for therapeutic targeting in ovarian and breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Rab coupling protein (RCP) is implicated in cancer invasion and metastasis.
  • Signal transducer and activator of transcription 3 (STAT3) is a known oncogenic factor involved in cancer progression.

Purpose of the Study:

  • To elucidate the critical role of STAT3 in RCP-induced cancer cell invasion.
  • To investigate the molecular mechanisms linking RCP, STAT3, and cancer metastasis.

Main Methods:

  • Immunohistochemistry on ovarian cancer tissues to correlate RCP and phospho-STAT3 (p-STAT3) expression.
  • In vitro studies involving cancer cell lines to assess RCP's effect on STAT3 phosphorylation.
  • Gene silencing and pharmacological inhibition of STAT3 to evaluate its impact on invasion.
  • Analysis of the β1 integrin/EGFR axis and downstream signaling pathways including NF-κB, Slug, and MT1-MMP.

Main Results:

  • High RCP and p-STAT3 expression correlated with lower survival rates in ovarian cancer patients.
  • RCP induced STAT3 phosphorylation in ovarian and breast cancer cells.
  • STAT3 inhibition significantly reduced RCP-induced cancer cell invasion.
  • The β1 integrin/EGFR axis was identified as crucial for RCP-induced STAT3 phosphorylation.
  • STAT3 activation of NF-κB led to Slug and MT1-MMP upregulation, promoting invasion.

Conclusions:

  • STAT3 is a critical mediator of RCP-induced cancer invasion and metastasis.
  • The β1 integrin/EGFR/STAT3/NF-κB/Slug/MT1-MMP axis represents a key pathway in RCP-driven cancer progression.
  • Targeting STAT3 may offer a therapeutic strategy against RCP-mediated invasion and metastasis.
Keywords:
Cancer cell invasionMT1-MMPRab coupling proteinSTAT3Slug

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