Rab8A promotes breast cancer progression by increasing surface expression of Tropomyosin-related kinase B

Yansong Liu1, Zhonghua Zhang2, Xuefeng Gao3

  • 1Department of Breast Disease, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Cancer Letters
|March 12, 2022
PubMed

Insights

Ras-related protein in brain (Rab) 8A promotes breast cancer growth by increasing Tropomyosin-related kinase B (TrkB) surface expression. Inhibiting Rab8A may halt cancer progression and improve patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Ras-related protein in brain (Rab) proteins are implicated in cancer progression.
  • Brain-derived neurotrophic factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) signaling are crucial in tumor development.

Purpose of the Study:

  • To investigate the interaction between Rab8A and TrkB in breast cancer progression.
  • To elucidate the role of Rab8A in regulating TrkB activity and downstream signaling pathways.

Main Methods:

  • Analysis of Rab8A expression in breast cancer tissues.
  • Knockdown of Rab8A and assessment of cancer cell proliferation, migration, and invasion.
  • Co-immunoprecipitation assays to study Rab8A-TrkB interaction.
  • Western blotting to evaluate AKT and ERK1/2 phosphorylation.
  • Treatment with TrkB inhibitor K252a.

Main Results:

  • Rab8A is upregulated in breast cancer tissues.
  • Rab8A knockdown inhibits breast cancer cell proliferation, migration, and invasion by reducing TrkB surface expression and suppressing AKT/ERK1/2 phosphorylation.
  • Rab8A interacts with TrkB, promoting its surface expression without affecting internalization.
  • BDNF upregulates Rab8A by inhibiting its degradation.
  • TrkB inhibition blocks Rab8A-induced cancer cell growth and signaling pathway activation.

Conclusions:

  • Rab8A, upregulated by BDNF, promotes breast cancer growth by enhancing TrkB surface expression and activating AKT/ERK1/2 signaling.
  • Targeting Rab8A presents a potential therapeutic strategy for inhibiting breast cancer progression.

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