Irisin is a myokine released during exercise (cleaved from FNDC5).
-It functions as a metabolic and anti-inflammatory signal, often counterbalancing obesity-associated adipokines (e.g., leptin).
-In cancer biology, irisin is predominantly anti-tumor, though effects can be context- and tissue-dependent.
Core Pathways Modulated by Irisin
1. AMPK ↑
-Effect: Energy stress signaling, metabolic checkpoint activation
-Cancer relevance:
-↓ mTOR activity
-↓ anabolic metabolism
-↑ autophagy-associated tumor suppression (early stages)
-Tumors: Breast, colorectal, liver
2. PI3K → AKT → mTOR ↓
-Effect: Reduced growth and survival signaling
-Cancer relevance:
-↓ proliferation
-↑ apoptosis sensitivity
-Opposes insulin / IGF-1 signaling
-Tumors: Breast, lung, pancreatic (preclinical)
3. MAPK / ERK ↓
-Effect: Reduced mitogenic signaling
-Cancer relevance:
-↓ cell cycle progression
-↓ migration
-Tumors: Osteosarcoma, breast
4. NF-κB ↓ (Anti-inflammatory)
-Effect: ↓ IL-6, TNF-α, COX-2
-Cancer relevance:
-Dampens chronic inflammation–driven oncogenesis
-Reduces tumor-promoting stromal signaling
-Tumors: Colorectal, liver
5. EMT / Metastasis ↓
-Effect: ↓ Snail, ↓ Twist, ↑ E-cadherin
-Cancer relevance:
-Reduced invasion and metastatic potential
-Tumors: Breast, lung
6. Oxidative Stress Modulation
-Effect: ↑ antioxidant defenses, improved mitochondrial efficiency
-Cancer relevance:
-Limits ROS-driven DNA damage
-Normal-cell protective bias
|