tribbles homolog 3
TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors.
TRIB3 encodes a pseudokinase—a kinase-like protein lacking catalytic activity but acting as a scaffold and signaling modulator. TRIB3 is strongly induced by cellular stress, particularly ER stress, nutrient deprivation, hypoxia, and oxidative stress, via ATF4/CHOP-dependent pathways.
Functionally UPREGULATED in many cancers, particularly in aggressive, hypoxic, or metabolically stressed tumors.
-Rarely mutated
-Induced by the tumor microenvironment
-Maintained by chronic stress signaling
TRIB3 is best viewed as a stress-selected dependency, not a classical oncogene.
High TRIB3 expression correlates with:
-EMT and invasive behavior
-Metastatic competence
-Poor prognosis in multiple solid tumors (e.g., breast, lung, colorectal, liver)
TRIB3 reports whether a tumor has entered a stress-adapted, survival-biased state. It is not used to choose a specific drug today.
TRIB3 is used as a clinical biomarker for Stress Adaptation
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