NUMB
Overview
NUMB is an endocytic adaptor protein that functions as a Notch pathway inhibitor by promoting NOTCH receptor degradation. NUMB can act as either a Notch inhibitor or modulator depending on cellular context. In oral squamous cell carcinoma (OSCC), NUMB copy gain was identified as part of the Notch pathway alteration signature affecting 66% of tumors.
Alterations observed in the corpus
- Copy gain observed in OSCC; categorized as a Notch pathway modulator contributing to the 66% prevalence of Notch pathway alterations when combined with NOTCH1 mutations, TP63 alterations, and MAML1 losses (40-tumor MD Anderson OSCC cohort) PMID:23619168
Cancer types (linked)
- HNSC (Head and Neck Squamous Cell Carcinoma) / OSCC: Copy gain detected by SNP array; the impact on Notch signaling (activating or inhibitory) depends on NUMB isoform and cellular context PMID:23619168
Co-occurrence and mutual exclusivity
- NUMB copy gain co-occurs with JAG1 and JAG2 gains and MAML1 losses in OSCC as part of the Notch pathway alteration pattern PMID:23619168
Therapeutic relevance
- No direct therapeutic implications identified in this study; the Notch pathway tumor-suppressor role in OSCC (as evidenced by functional NOTCH1 activation suppressing growth) would suggest that NUMB gains potentially reflect counter-regulatory Notch modulation PMID:23619168
Open questions
- Whether NUMB copy gain in OSCC activates or inhibits Notch signaling in the specific OSCC context has not been functionally resolved; the interpretation depends on which NUMB isoforms are expressed PMID:23619168
Sources
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