title: Hypoxia, therapeutic resistance, and sphingosine 1-phosphate.
abstract: Hypoxia, defined as a poor oxygenation, has been long recognized as a hallmark of solid tumors and a negative prognostic factor for response to therapeutics and survival of patients. Cancer cells have evolved biochemical mechanisms that allow them to react and adapt to hypoxia. At the cellular level, this adaptation is under the control of two related transcription factors, HIF-1 and HIF-2 (hypoxia-inducible factor), that respond rapidly to decreased oxygen levels to activate the expression of a broad range of genes promoting neoangiogenesis, glycolysis, metastasis, increased tumor growth, and resistance to treatments. 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-1 or HIF-2 activity. In this review, we will focus on how the inhibition/neutralization of the SphK1/S1P signaling could be exploited for cancer therapy.
authors.affiliation: CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France; Université de Toulouse, Toulouse, France. olivier.cuvillier@inserm.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Cuvillier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ader
authors.forename: Pierre
authors.initials: P
authors.lastname: Bouquerel
authors.forename: Leyre
authors.initials: L
authors.lastname: Brizuela
authors.forename: Cécile
authors.initials: C
authors.lastname: Gstalder
authors.forename: Bernard
authors.initials: B
authors.lastname: Malavaud
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000860:Hypoxia; D008246:Lysophospholipids / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate