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Gap junction beta-4 accelerates cell cycle progression and metastasis through MET-AKT activation in pancreatic cancer

Joji Muramatsu1, Yohei Arihara1, Makoto Yoshida1

  • 1Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Cancer Science
|February 11, 2024
PubMed

Insights

Pancreatic cancer shows elevated gap junction beta-4 (GJB4) protein, negatively impacting survival. Targeting the GJB4-MET pathway offers a potential new therapeutic strategy for this poor-prognosis cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Pancreatic cancer has a dismal prognosis despite advances in therapy.
  • Gap junction proteins are emerging as potential therapeutic targets in cancer.
  • The specific role of gap junction beta-4 (GJB4) in pancreatic cancer is currently unknown.

Purpose of the Study:

  • To investigate the role and prognostic significance of GJB4 in pancreatic cancer.
  • To explore the therapeutic potential of targeting GJB4 in pancreatic cancer models.

Main Methods:

  • Bioinformatic analysis of GJB4 transcript levels in pancreatic cancer tissues versus normal tissues.
  • Assessment of GJB4 expression as a prognostic factor.
  • In vitro studies involving GJB4 knockdown and overexpression in pancreatic cancer cell lines.
  • In vivo studies using a mouse xenograft model.
  • Investigation of the GJB4-MET-AKT signaling pathway.

Main Results:

  • Pancreatic cancer tissues exhibit higher GJB4 transcript levels than normal tissues, correlating with reduced overall survival.
  • High nuclear GJB4 expression is a negative prognostic indicator.
  • GJB4 knockdown induces G0/G1 cell cycle arrest, reduces proliferation, and suppresses metastasis.
  • GJB4 overexpression enhances proliferation, migration, and invasion, effects reversed by MET inhibition.
  • GJB4 suppression inhibits tumor growth in vivo and downregulates MET-AKT signaling.

Conclusions:

  • Elevated GJB4 expression is a significant negative prognostic factor in pancreatic cancer.
  • The GJB4-MET axis plays a crucial role in pancreatic cancer progression.
  • Targeting the GJB4-MET axis presents a promising therapeutic strategy for pancreatic cancer.
Keywords:
GJB4MET–AKTcell cycle arrestmetastasispancreatic cancer

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