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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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TRIB3 Modulates PPARγ-Mediated Growth Inhibition by Interfering with the MLL Complex in Breast Cancer Cells

Miguel Hernández-Quiles1, Rosalie Baak1, Alba Orea-Soufi2,3

  • 1Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, CG, The Netherlands.

International Journal of Molecular Sciences
|September 23, 2022
PubMed

Insights

Tribbles pseudokinase 3 (TRIB3) epigenetically regulates PPARγ expression in breast cancer. TRIB3 levels predict response to PPARγ ligand therapy, offering a potential biomarker for treatment success.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Aberrant protein activity drives cancer initiation, progression, and therapy resistance.
  • Tribbles pseudokinase 3 (TRIB3) is frequently dysregulated in cancer and linked to breast cancer metastasis.
  • The precise mechanisms of TRIB3's role in cancer remain largely undefined.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which TRIB3 influences breast cancer progression.
  • To investigate the relationship between TRIB3 and the transcription factor PPARγ in breast cancer.
  • To assess the potential of TRIB3 as a predictive biomarker for PPARγ ligand therapy.

Main Methods:

  • Proteomics and phosphoproteomics analyses.
  • Biochemical assays to study protein interactions.
  • Analysis of TRIB3's effect on PPARγ mRNA expression and epigenetic modifications.
  • Assessment of TRIB3's impact on breast cancer cell proliferation in response to PPARγ ligands.

Main Results:

  • TRIB3 was found to regulate PPARγ expression in breast cancer cells.
  • TRIB3 interferes with the MLL complex, reducing H3K4 trimethylation at the PPARG locus.
  • Overexpression of TRIB3 diminishes the antiproliferative effects of PPARγ ligands, while TRIB3 knockdown enhances them.

Conclusions:

  • TRIB3 plays a role in epigenetic gene regulation within breast cancer.
  • TRIB3 levels may serve as a predictive marker for the efficacy of PPARγ ligand treatments.
  • Targeting TRIB3 or utilizing it as a biomarker could offer new therapeutic strategies for breast cancer.
Keywords:
MLL–WRAD complexPPARγTribblesbreast cancerepigenetics

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