Tumorigenic implication Cancer type HIF mediation Effect Reference TSC niche Neuroblastoma   ↑Tumorigenic fraction Das B et al,2008 Rhabdomyosarcoma GBM xenograft   ↑ Endothelial cell migration Bao S et al, 2006 Cellular adaptations Hepatoma HIF-1a  ↑Hexokinase II Gwak G et al, 2005 Mathupala SP et al , 2001 Wilms tumors HIF-1α ↑GLUT-1, CA9 Dungwa, J.V et al, 2011 Rhabdomyosarcoma HIF-1α ↑ GLUT-1, aldolase Kilic, M et al, 2007 Ewings’ sarcoma HIF-1α B-cell non-Hodgkin lymphomas HIF1α, HIF2α ↑ LDH5 Giatromanolaki A  et al ,2008 Angiogenesis Wilms’ tumor HIF-1α ↑ VEGF Karth J et al, 2000 Dungwa JV et al, 2011 Rhabdomyosarcoma no ↑ IL-8 Wysoczynski  M et al, 2010. Anaplastic large-cell lymphoma HIF-1a ↑ VEGF Dejean, E., et al 2011 Neuroblastoma   ↑ VEGF Rössler J et al, 1999  Jögi A et al, 2004 GBM xenograft TSC   ↑ VEGF secretion Bao S et al, 2006 Apoptosis evasion Rhabdomyosarcoma HIF-1α ↑ Glucose uptake Kilic M et al, 2007 Ewings’ sarcoma HIF-1α Hepatoma HIF-1a  ↑ Glucose uptake Gwak G et al, 2005  Invasion and metastasis Glioma HIF-1a ↑Proteolytic activity of matrix melloproteinases degradation of the extracellular matrix Fujiwara S et al, 2007 Hepatoma   Miyoshi A et al, 2006 Glioma HIF-1a ↑ Cell migration Zagzag D et al, 2003 Ewings’ sarcoma HIF-1a ↑ Invasiveness and soft-agar colony formation Aryee D et al, 2010 Neuroblastoma   Cell dedifferentiation, tumor heterogenicity , increased malignancy Jogi, A et al, 2003 Medulloblastoma HIF-1α Activation of the Notch signaling pathway,↑ stem cell viability and expansion Pistollato F et al , 2010

Table 1: Summary of pediatric data linking hypoxia to childhood malignancies.