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TRIB3 suppresses tumorigenesis by controlling mTORC2/AKT/FOXO signaling

María Salazar1, Mar Lorente1, Elena García-Taboada2

  • 1Department of Biochemistry and Molecular Biology I; School of Biology; Complutense University; Madrid, Spain; Instituto de Investigaciones Sanitarias San Carlos (IdISSC); Madrid, Spain.

Molecular & Cellular Oncology
|June 17, 2016
PubMed

Insights

Tribbles pseudokinase 3 (TRIB3) acts as a tumor suppressor by disrupting the AKT signaling pathway. This protein impacts the mammalian target of rapamycin complex 2 (mTORC2) and Forkhead box O3 (FOXO3) to inhibit cancer growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tribbles pseudokinase 3 (TRIB3) is implicated in various cellular processes.
  • The AKT signaling pathway is frequently dysregulated in cancer.
  • Mammalian target of rapamycin complex 2 (mTORC2) and Forkhead box O3 (FOXO3) are critical regulators of cell survival and proliferation.

Purpose of the Study:

  • To elucidate the role of Tribbles pseudokinase 3 (TRIB3) in tumor suppression.
  • To investigate the molecular mechanisms by which TRIB3 exerts its tumor suppressor function.
  • To determine the interplay between TRIB3, AKT, mTORC2, and FOXO3.

Main Methods:

  • Western blotting to assess protein phosphorylation and expression.
  • Immunoprecipitation assays to study protein interactions.
  • Cell-based assays to evaluate cell proliferation and apoptosis.

Main Results:

  • TRIB3 demonstrates a significant tumor suppressor role.
  • TRIB3 dysregulates the phosphorylation of v-akt murine thymoma viral oncogene homolog (AKT) via mTORC2.
  • This leads to hyperphosphorylation and inactivation of the transcription factor Forkhead box O3 (FOXO3).

Conclusions:

  • TRIB3 functions as a tumor suppressor by inhibiting the AKT/mTORC2/FOXO3 signaling axis.
  • Understanding this pathway provides potential therapeutic targets for cancer treatment.
  • TRIB3's role highlights a novel mechanism in cancer regulation.
Keywords:
PTENTribbles pseudokinasesanimal models of cancerprostate cancerskin carcinogenesis

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