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When the Sphingosine Kinase 1/Sphingosine 1-Phosphate Pathway Meets Hypoxia Signaling: New Targets for Cancer Therapy

¹ CNRS, Institut de Pharmacologie et de Biologie Structurale; ² Université de Toulouse, UPS, IPBS; and ³ CHU Toulouse, Hôpital Rangueil, Toulouse, France

Requests for reprints: Olivier Cuvillier, CNRS UMR 5089, 31077 Toulouse, France. Phone: 33-5-61-17-55-13; Fax: 33-5-61-17-58-71; E-mail: olivier.cuvillier{at}ipbs.fr.

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 1 (HIF-1) 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-1 activity under hypoxic conditions. Here, we consider how the SphK1/S1P signaling pathway could represent a very important target for therapeutic intervention in cancer. [Cancer Res 2009;69(9):3723–6]