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Table I.

Dual role of Notch signaling in cancer

Tumor type Role of Notch signaling Genes mutated Putative or observed effect References 
T-ALL Oncogene NOTCH1 Ligand independent activation Ellisen et al., 1991  
  FBXW7 Stabilization of N1-IC Weng et al., 2004  
    Malyukova et al., 2007  
    Maser et al., 2007  
    O’Neil et al., 2007  
    Thompson et al., 2007  
CLL Oncogene NOTCH1 Stabilization of N1-IC Fabbri et al., 2011  
   Correlated with reduced survival Puente et al., 2011  
NSCLC Oncogene NOTCH1 Stabilization of N1-IC Westhoff et al., 2009  
   Correlated with reduced survival  
PDAC Oncogene none Loss of NOTCH1 decreased tumor latency Hanlon et al., 2010  
 Tumor suppressor  Loss of NOTCH2 increased tumor latency Mazur et al., 2010  
HCC Tumor suppressor none Endogenous activation of Notch induces growth arrest and apoptosis Viatour et al., 2011  
   Activated Notch pathway correlated with better survival  
CMML Tumor suppressor NCSTN Loss of function mutations Klinakis et al., 2011  
  MAML1 Activated Notch signaling inhibits myeloid progenitor differentiation.  
  APH1A  
  NOTCH2   
HNSCC Tumor suppressor NOTCH1 Truncated or ligand-binding inefficient receptors Stransky et al., 2011  
  NOTCH2 Predicted to impair differentiation Agrawal et al., 2011  
  NOTCH3   
B-ALL Tumor suppressor none Endogenous or exogenous activation of Notch induces growth arrest and apoptosis Zweidler-McKay et al., 2005  
Tumor type Role of Notch signaling Genes mutated Putative or observed effect References 
T-ALL Oncogene NOTCH1 Ligand independent activation Ellisen et al., 1991  
  FBXW7 Stabilization of N1-IC Weng et al., 2004  
    Malyukova et al., 2007  
    Maser et al., 2007  
    O’Neil et al., 2007  
    Thompson et al., 2007  
CLL Oncogene NOTCH1 Stabilization of N1-IC Fabbri et al., 2011  
   Correlated with reduced survival Puente et al., 2011  
NSCLC Oncogene NOTCH1 Stabilization of N1-IC Westhoff et al., 2009  
   Correlated with reduced survival  
PDAC Oncogene none Loss of NOTCH1 decreased tumor latency Hanlon et al., 2010  
 Tumor suppressor  Loss of NOTCH2 increased tumor latency Mazur et al., 2010  
HCC Tumor suppressor none Endogenous activation of Notch induces growth arrest and apoptosis Viatour et al., 2011  
   Activated Notch pathway correlated with better survival  
CMML Tumor suppressor NCSTN Loss of function mutations Klinakis et al., 2011  
  MAML1 Activated Notch signaling inhibits myeloid progenitor differentiation.  
  APH1A  
  NOTCH2   
HNSCC Tumor suppressor NOTCH1 Truncated or ligand-binding inefficient receptors Stransky et al., 2011  
  NOTCH2 Predicted to impair differentiation Agrawal et al., 2011  
  NOTCH3   
B-ALL Tumor suppressor none Endogenous or exogenous activation of Notch induces growth arrest and apoptosis Zweidler-McKay et al., 2005  

PDAC: pancreatic ductal adenocarcinoma; B-ALL: B cell acute lymphoblastic leukemia.

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