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Regulation of autophagy by Rab27B in colorectal cancer

Sahida Afroz1, Ranjan Preet1, Vikalp Vishwakarma1

  • 1Department of Molecular Biosciences, University of Kansas, Lawrence, KS, USA.

The International Journal of Biochemistry & Cell Biology
|November 14, 2024
PubMed

Insights

Rab27B regulates autophagy in colorectal cancer (CRC) by controlling vesicle trafficking. Its depletion blocks autophagy flux, impacting tumor growth and suggesting Rab27B as a potential therapeutic target for CRC.

Area of Science:

  • Cell Biology
  • Oncology
  • Cancer Research

Background:

  • Autophagy is a cellular recycling process crucial in colorectal cancer (CRC) development, immune response, and treatment resistance.
  • The small GTPase Rab27B's role in CRC autophagy remains largely unexplored.

Purpose of the Study:

  • To investigate the function of Rab27B in regulating autophagy within colorectal cancer cells.
  • To determine the impact of Rab27B on CRC cell growth and tumorigenesis.

Main Methods:

  • Depletion of Rab27B in CRC cells.
  • Analysis of autophagy markers and vesicle accumulation.
  • Image analysis to assess autophagy flux, specifically autophagosome-lysosome fusion.
  • In vitro 2D and 3D cell growth assays.
  • In vivo tumorigenesis studies.

Main Results:

  • Rab27B depletion led to abnormal accumulation of autophagy vesicles and increased autophagy markers, indicating dysregulated autophagy.
  • Loss of Rab27B blocked autophagy flux at the autophagosome-lysosome fusion stage.
  • While Rab27B-deficient cells grew normally in 2D cultures, their 3D in vitro growth and in vivo tumorigenesis were significantly impaired.

Conclusions:

  • Rab27B plays a critical role in the autophagy trafficking process in colorectal cancer.
  • Rab27B is essential for efficient autophagy flux and impacts CRC cell growth and tumor formation.
  • Rab27B represents a promising novel therapeutic target for colorectal cancer treatment.
Keywords:
AutophagyColorectal cancerRab27B

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