Related Experiment Video
Updated: Apr 25, 2026
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Loss of Tribbles pseudokinase-3 promotes Akt-driven tumorigenesis via FOXO inactivation
M Salazar1, M Lorente1, E García-Taboada2
11] Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain [2] Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain.
Abstract:
Tribbles pseudokinase-3 (TRIB3) has been proposed to act as an inhibitor of AKT although the precise molecular basis of this activity and whether the loss of TRIB3 contributes to cancer initiation and progression remain to be clarified. In this study, by using a wide array of in vitro and in vivo approaches, including a Trib3 knockout mouse, we demonstrate that TRIB3 has a tumor-suppressing role. We also find that the mechanism by which TRIB3 loss enhances tumorigenesis relies on the dysregulation of the phosphorylation of AKT by the mTORC2 complex, which leads to an enhanced phosphorylation of AKT on Ser473 and the subsequent hyperphosphorylation and inactivation of the transcription factor FOXO3. These observations support the notion that loss of TRIB3 is associated with a more aggressive phenotype in various types of tumors by enhancing the activity of the mTORC2/AKT/FOXO axis.
Insights
Tribbles pseudokinase-3 (TRIB3) suppresses tumors by regulating AKT phosphorylation. Loss of TRIB3 promotes cancer by disrupting the mTORC2/AKT/FOXO signaling pathway, leading to aggressive tumor phenotypes.
Area of Science:
- Molecular biology
- Cancer research
- Signal transduction
Background:
- Tribbles pseudokinase-3 (TRIB3) is suggested to inhibit AKT, but its role in cancer and the molecular mechanisms are unclear.
- Understanding TRIB3's function is crucial for cancer therapy development.
Purpose of the Study:
- To elucidate the precise molecular mechanism of TRIB3's interaction with AKT.
- To determine if TRIB3 loss contributes to cancer initiation and progression.
- To investigate the role of TRIB3 in tumor suppression.
Main Methods:
- In vitro biochemical assays.
- In vivo studies using a Trib3 knockout mouse model.
- Analysis of signaling pathways including mTORC2, AKT, and FOXO3 phosphorylation.
Main Results:
- TRIB3 demonstrates a tumor-suppressing role.
- Loss of TRIB3 enhances tumorigenesis through dysregulation of AKT phosphorylation by mTORC2.
- AKT phosphorylation at Ser473 is increased, leading to FOXO3 hyperphosphorylation and inactivation.
Conclusions:
- TRIB3 loss is associated with aggressive tumor phenotypes.
- The mTORC2/AKT/FOXO axis is a key pathway through which TRIB3 exerts its tumor-suppressive function.
- Targeting this axis could offer therapeutic strategies for TRIB3-deficient cancers.
More Related Videos
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
07:16Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:12Loss of Tumor Suppressor Gene Functions
02:23Abnormal Proliferation