Leptin is an adipokine elevated in obesity.
Many tumors overexpress the leptin receptor (Ob-R), creating autocrine/paracrine signaling loops.
Leptin acts as a pro-oncogenic signal integrator, linking:
-Adiposity
-Inflammation
-Growth factor signaling
-Metabolic reprogramming
1.Circulating leptin (systemic)
-Upregulated in obesity, which strongly correlates with higher cancer risk and worse outcomes in several tumor types.
-This creates a permissive, pro-tumor systemic environment.
2.Tumor leptin receptor (Ob-R) expression
-Frequently upregulated in tumors (and tumor stroma), even when circulating leptin is only modestly elevated.
-Leads to hypersensitivity to leptin.
3.Autocrine/paracrine leptin production
-Many tumors produce leptin locally, independent of adipose tissue.
-Establishes a self-reinforcing growth loop.
4.Downstream leptin signaling
-Consistently upregulated:
-JAK2 → STAT3
-PI3K → AKT → mTOR
-APK/ERK
-NF-κB
-These pathways drive proliferation, survival, angiogenesis, EMT, and therapy resistance.
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