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Inhibition of oncogenic Src induces FABP4-mediated lipolysis via PPARγ activation exerting cancer growth suppression

Tuyen N M Hua1, Min-Kyu Kim1, Vu T A Vo1

  • 1Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 26426, Republic of Korea; Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 26426, Republic of Korea; Mitohormesis Research Center, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 26426, Republic of Korea.

Ebiomedicine
|February 14, 2019
PubMed
Abstract

Insights

Inhibiting oncogenic Src promotes cancer cell lipolysis and reduces tumor growth by activating PPARγ and FABP4. This highlights Src

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • c-Src is a known oncogene involved in tumorigenic signaling.
  • Its role in metabolic function, particularly lipid metabolism, is less understood.
  • Prior research indicated c-Src influences glucose metabolism.

Purpose of the Study:

  • To investigate the function of c-Src in modulating lipid metabolism in cancer.
  • To explore the mechanisms by which c-Src affects cancer cell lipolysis and growth.

Main Methods:

  • Utilized oil-red O staining, cell growth assays, and xenograft models to assess lipid content and treatment effects.
  • Evaluated gene expression via immunoblotting and RT-PCR.
  • Assessed peroxisome proliferator-activated receptor gamma (PPARγ) activity, reactive oxygen species (ROS) levels, and oxygen consumption rates.
  • Examined clinical relevance using patient samples and public databases.

Main Results:

  • Src inhibition led to increased lipolysis and intracellular ROS.
  • Derepressed PPARγ transcriptional activity upon Src inhibition induced fatty acid binding protein 4 (FABP4) expression.
  • Reduced lipid droplets and decreased tumor growth were observed following Src inhibition.
  • A reverse correlation between Src and FABP4 was found in lung cancer patient samples.

Conclusions:

  • Oncogenic Src regulates both cellular signaling and metabolic plasticity to drive cancer progression.
  • Src inhibition promotes lipolysis and impacts cancer growth, suggesting a therapeutic target.
  • Upregulation of lipolytic genes correlates with better cancer patient prognosis.
Keywords:
FABP4LipidLung cancerPPARγSrc

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