When the sphingosine kinase 1/sphingosine 1-phosphate pathway meets hypoxia signaling: new targets for cancer therapy.
The reduction in the normal level of tissue oxygen tension or hypoxia is a characteristic of solid tumors that triggers the activation of signaling pathways promoting neovascularization, metastasis, increased tumor growth, and resistance to treatments. The activation of the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) has been identified as the master mechanism of adaptation to hypoxia. In a recent study, we identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway, which elicits various cellular processes including cell proliferation, cell survival, or angiogenesis, as a new modulator of HIF-1alpha activity under hypoxic conditions. Here, we consider how the SphK1/S1P signaling pathway could represent a very important target for therapeutic intervention in cancer.
Ader
Isabelle
I
CNRS, Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, UPS, IPBS, Hôpital Rangueil, Toulouse, France.
Malavaud
Bernard
B
Cuvillier
Olivier
O
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D016503:Drug Delivery Systems; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000099157:Sphingosine Kinase
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate