TRIB3 Involvement in Metabolic and Cancer Pathways

Tribbles homolog 3 (TRIB3) is a pseudokinase that functions as a molecular scaffold across multiple cellular compartments, integrating metabolic cues with stress responses and oncogenic signalling. In metabolic tissues, TRIB3 regulates insulin-mediated Akt phosphorylation, modulates endoplasmic reticulum stress via the ATF4 axis and influences lipid homeostasis in adipocytes. Perturbation of these pathways by altered TRIB3 expression can affect glucose uptake, triglyceride storage and the balance between cell proliferation and differentiation. In cancer, TRIB3 exerts context-dependent roles, interacting with key regulators such as AKT1, Notch1, HER2 and β-catenin to influence tumour cell survival, invasion and metastasis. Elevated TRIB3 levels have been linked to poor prognosis in several solid tumours, where it can promote immune evasion and radioresistance, whereas in certain subtypes of luminal breast cancer it correlates with improved treatment response. Collectively, TRIB3 emerges as a critical node connecting metabolic stress and oncogenic pathways, with implications for therapeutic targeting in metabolic disorders and malignancies.

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TRIB3 Involvement in Metabolic and Cancer Pathways publication trend

The graph below shows the total number of articles in trib3 involvement in metabolic and cancer pathways across all publications each year (not limited to Nature Index journals).

Technical terms

Pseudokinase: A protein structurally similar to kinases but lacking catalytic phosphotransfer activity, often functioning as a scaffold or regulator.

Lipidomics: Large-scale study of cellular lipid profiles and their dynamic changes under physiological or pathological conditions.

Transcriptomics: Comprehensive analysis of RNA transcripts to assess gene expression patterns.

Phosphoproteomics: Investigation of phosphorylated proteins to map signalling networks and post-translational modifications.

Prognostic biomarker: A measurable indicator that predicts the likely outcome or progression of a disease.

References

1. The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo. Molecular Metabolism (2023).
2. TRB3 Inhibits the Transcriptional Activation of Stress-regulated Genes by a Negative Feedback on the ATF4 Pathway*. Journal of Biological Chemistry (2007).
3. TRIB3, as a robust prognostic biomarker for HNSC, is associated with poor immune infiltration and cancer cell immune evasion. Frontiers in Immunology (2024).
4. Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation. Cancers (2019).
5. The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer. Cancers (2021).
6. Parishin B blocking TRIB3-AKT1 interaction inhibits breast cancer lung metastasis. Frontiers in Pharmacology (2025).