title: Hypoxia-inducible factors and sphingosine 1-phosphate signaling.
abstract: Hypoxia, defined as reduced tissue oxygen concentration, is a characteristic of solid tumors and is an indicator of unfavorable diagnosis in patients. At the cellular level, the adaptation to hypoxia is under the control of two related transcription factors, HIF-1α and HIF-2α (Hypoxia-Inducible Factor), which activate expression of genes promoting angiogenesis, metastasis, increased tumor growth and resistance to treatments. A role for HIF-1α and HIF-2α is also emerging in hematologic malignancies such as lymphoma and l eukemia. Recent studies have identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway - which elicits various cellular processes including cell proliferation, cell survival or angiogenesis - as a new regulator of HIF-1α or HIF-2α activity. This review will consider how targeting the SphK1/S1P signaling could represent an attractive strategy for therapeutic intervention in cancer.
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France. cuvillio@me.com
authors.forename: Olivier
authors.initials: O
authors.lastname: Cuvillier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ader
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; D000099162:Endothelial PAS Domain-Containing Protein 1; C060506:sphingosine 1-phosphate