FABP5 suppresses colorectal cancer progression via mTOR-mediated autophagy by decreasing FASN expression

Mujie Ye1, Chunhua Hu1, Tiaotiao Chen1

  • 1Department of Geriatric Gastroenterology, Neuroendocrine Tumor Center, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Institute of Neuroendocrine Tumor, Nanjing Medical University, Nanjing, China.

Insights

Fatty acid-binding protein 5 (FABP5) suppresses colorectal cancer (CRC) progression by inhibiting proliferation and tumor growth. Its downregulation in CRC suggests FABP5 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Lipid metabolism is crucial in cancer development, particularly in digestive system tumors like colorectal cancer (CRC).
  • Fatty acid-binding protein 5 (FABP5) role in CRC remains to be fully elucidated.

Purpose of the Study:

  • Investigate the function of FABP5 in colorectal cancer (CRC).
  • Elucidate the underlying molecular mechanisms of FABP5's action in CRC.
  • Identify potential therapeutic targets for CRC intervention.

Main Methods:

  • Gene expression analysis in CRC tissues.
  • In vitro functional assays (proliferation, colony formation, migration, invasion).
  • In vivo tumor growth studies.
  • Mechanistic studies involving protein-protein interactions, ubiquitination assays, and signaling pathway analysis.
  • Pharmacological inhibition of FASN.

Main Results:

  • FABP5 was significantly downregulated in CRC.
  • FABP5 exhibited inhibitory effects on CRC cell proliferation, colony formation, migration, invasion, and tumor growth.
  • FABP5 interacted with FASN, promoting its degradation via the ubiquitin-proteasome pathway, reducing lipid accumulation, suppressing mTOR signaling, and enhancing autophagy.
  • Orlistat (FASN inhibitor) demonstrated anti-cancer effects.
  • ALKBH5 positively regulated FABP5 expression through an m6A-independent mechanism.

Conclusions:

  • FABP5 acts as a tumor suppressor in CRC.
  • The ALKBH5/FABP5/FASN/mTOR axis is critical in CRC progression.
  • Targeting this axis offers potential therapeutic strategies for CRC.

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