NOTCH1
🔍 Overview
NOTCH1 encodes a transmembrane receptor involved in cell-cell communication. Upon ligand binding (e.g., Jagged, Delta), NOTCH1 undergoes cleavage, releasing the Notch intracellular domain (NICD), which translocates to the nucleus and regulates gene transcription.
⚠️ Dual Role in Cancer
NOTCH1 can act as either:
- An oncogene (e.g., T-cell acute lymphoblastic leukemia)
- A tumor suppressor (e.g., squamous cell carcinomas)
📊 Prevalence
| Cancer Type | NOTCH1 Role | Mutation Frequency |
|---|---|---|
| T-ALL | Oncogene | ~50–60% |
| Chronic lymphocytic leukemia (CLL) | Oncogene | ~10–15% |
| Squamous cell skin cancer | Tumor suppressor | ~40–60% |
| Head and neck SCC | Tumor suppressor | ~15–20% |
| Esophageal SCC | Tumor suppressor | ~10–20% |
⚙️ Mechanism
- Activating mutations → Constitutively active NICD → continuous gene transcription → proliferation (e.g., in T-ALL)
- Loss-of-function mutations → Disrupted differentiation → tumorigenesis (e.g., in skin cancer)