UNDERSTANDING SPHINGOSINE 1-PHOSPHATE METABOLISM IN CANCER & AGING



Sphingolipids have long been known to play important roles in cellular metabolism and membrane biology, but the notion of sphingolipids as cellular signaling molecules has gained recognition only the last two decades. Bioactive sphingolipids, including ceramide, sphingosine and sphingosine 1-phosphate (S1P) are now appreciated as key regulators of multiple cellular processes, including cell proliferation, differentiation, apoptosis, and immune responses. Our Lab is studying the role of S1P metabolism in cancer and aging.




RECENT NEWS



July 6-7, 2017
PIREPRED consortium meeting & Scientific Workshop in Bilbao on genetics and therapeutic approaches on rare diseases

Stacks Image 549




April 23-25, 2017
French Society of Angiogenesis

On behalf of the French Society of Angiogenesis, the Lab co-organizes the 7th Meeting of the French Society of Angiogenesis in Toulouse from April 23 to April 25.
Read more
Stacks Image 106


March 28, 2017
Chromosome segregation and mitotic progression are regulated by S1P5 signaling

Our findings describe a novel unexpected function for S1P signaling and the underlying molecular mechanism by which it regulates mitotic progression and chromosome segregation.
by Guillaume Andrieu et al. in Science Signaling
Read more


Stacks Image 386




Cover story:
Mitotic signals through S1P
Targeting the signaling lipid S1P might suppress tumor growth by slowing mitosis



Oct 5, 2016
PIREPRED consortium meeting in Zaragoza

Stacks Image 116
Hospitales y centros de investigación de ambos lados del Pirineo se unen para mejorar los programas de cribado neonatal
Pirepred permitirá que hospitales y centros de investigación de ambos lados del Pirineo se unan para mejorar los programas de cribado neonatal. Así, desarrollará herramientas bioinformáticas de diagnóstico genético que ayuden a un pronóstico personalizado lo antes posible. El proyecto europeo está dotado con 827.000 euros para tres años.




Stacks Image 122


Des hôpitaux et des centres de recherche des deux côtés des Pyrénées s’associent pour améliorer les programmes de dépistage néonatal
Le projet Pirepred va permettre à des hôpitaux et des centres de recherche des deux côtés des Pyrénées de se réunir pour améliorer les programmes de dépistage néonatal.
Ainsi, de nouveaux outils de diagnostic génétique bioinformatiques seront développés pour permettre une prévision personnalisée des maladies néonatales dès que possible. Ce projet européen est doté de 827.000 euros pour trois ans.



July 20, 2016
FTY720 (Fingolimod) inhibits HIF-1 and HIF-2 signaling, and sensitizes to chemotherapy in renal cell carcinoma
Our findings establish that FTY720 (Fingolimod) blocks HIF-1 and HIF-2 accumulation in cell and animal model of ccRCC and sensitize to chemotherapy.
by Cécile Gstalder et al. in Mol Cancer Ther
Read more



Stacks Image 137


May 11, 2016
The Sphingolipid in Cancer & Aging Lab is a partner of the PIREPRED consortium funded by POCTEFA action
Este proyecto está cofinanciado por el Fondo Europe de Desarrollo Regional (FEDER)/ Ce projet est cofinancé par le Fonds Européen de Développement Régional (FEDER).
Read more

Stacks Image 513

January 26, 2016
The SphK1/S1P/S1P1 signaling regulates HIF-2α activity in cancer
Our work establishes the essential role of an autocrine signaling involving S1P1 in the regulation of HIF-2α expression and activity in cancer by the SphK1/S1P signaling. These findings demonstrate that S1P may act as a canonical regulator of HIF-2α expression in ccRCC, giving support to its inhibition as a therapeutic strategy that could contribute to reduce HIF-2 activity in ccRCC.
by Pierre Bouquerel et al. in Oncogenesis
Read more



Stacks Image 163

July 8, 2015
Cécile Gstalder PhD thesis defense
Cécile defended her PhD thesis, entitled ‘Rôle de la voie sphingosine kinase 1/sphingosine 1-phosphate
dans l’adaptation à l’hypoxie intratumorale
des adénocarcinomes rénaux à cellules claires
’. Prof. Catherine Muller (University of Toulouse) acted as the chair of the examination committee. The three discussants were: Prof. Alain Ravaud from the University of Bordeaux, Dr. François Vallette from University of Nantes and Dr. Fabrice Soncin from the University of Lille.
We wish Cécile all the best for her future career!


June 18-19, 2015
NEUROMED consortium final meeting & closing workshop in Barcelona


Stacks Image 187

May 12-17, 2015
Cécile Gstalder, PhD student, will present her work at the Keystone Symposia on hypoxia, Dublin (Ireland)

Stacks Image 198

May 1, 2015
Catherine Mazerolles
It is with profound sadness that we report the death of our colleague Dr Catherine Mazerolles on April 28. She was 55.
Catherine, uropathologist at the Hôpitaux de Toulouse, was a member of our research team for over ten years. She will be sorely missed.


March 5-6, 2015
The NEUROMED consortium meets at IPBS
Next meeting in Barcelona, June 18-19

Stacks Image 220
January 12, 2015
S1P as a therapeutic target to tackle hypoxia
Our study demonstrates preclinical proof of concept in mice bearing orthotopic prostate tumors that a strategy aimed at neutralizing S1P with a monoclonal antibody could reduce intratumoral hypoxia and associated vascular network malfunction by enhancing blood perfusion to significantly improve delivery and efficacy of docetaxel, the standard chemotherapy for prostate cancer. Our findings encourage further clinical studies to assess whether optimized scheduling of anti-S1P treatment provide evidence for vessel normalization in cancer patients to identify those who might be benefit from a combination therapy with chemotherapy or radiotherapy.
by Isabelle Ader et al. in Oncotarget
Read more





Stacks Image 231

July 9, 2014
The Sphingolipid in Cancer & Aging Lab is a partner of the NEUROMED consortium funded by SUDOE action
Read more
El periodico de aragon


Stacks Image 244

April 14, 2014
A dual role for S1P in prostate bone microenvironment
Osteoblast-borne S1P promotes osteoblastic differentiation, and proliferation and survival of prostate cancer cells uncovering the importance of S1P in the bone microenvironment, which may open a novel area of study for the treatment of prostate bone metastasis by targeting S1P.
by Leyre Brizuela et al. in Mol Oncol
Read more



Stacks Image 257

January 27, 2014
S1P as a biomarker of Alzheimer’s Disease
Analysis of 56 human Alzheimer’s Disease human brains revealed a decrease in SphK1 expression whereas S1P lyase expression was increased, highlighting the importance of S1P and suggesting the existence of a global deregulation of S1P signaling in this neurodegenerative disease.
by Johnatan Ceccom et al. in Acta Neuropathologica Comm
Read more




Stacks Image 268

May 10, 2013
Interview of Olivier Cuvillier by the french newspaper ‘Le Figaro’ about chemoprevention and cancer
Read more


Stacks Image 279

March 11, 2013
The Innovative Models Initiative (IMODI) consortium laureate of the French Government’s Investing for the Future programme ‘Programme d’Investissements d’Avenir’.
The Sphingolipid in Cancer & Aging Lab is a member of the IMODI consortium for the characterization and validation of novel prostate cancer cell models
Read more

Stacks Image 290



QUESTIONS ? GET IN TOUCH.

CALL:
+33 561 17 55 13

WRITE:
IPBS, Institute of Pharmacology and Structural Biology
CNRS UMR 5089
205 Route de Narbonne - BP 64182
31077 Toulouse Cedex 4, France






PUBLICATIONS

Sphingosine 1-phosphate signaling through its receptor S1P5 promotes chromosome segregation and mitotic progression
Andrieu G, Ledoux A, Branka S, Bocquet M, Walzer T, Kasahara, K, Inagaki M, Sabbadini RA, Cuvillier O*, Hatzoglou A*
Science Signaling, 10 (2017) eaah4007
Abstract

The therapeutic potential of HIF-2 antagonism in Renal Cell Carcinoma
Cuvillier O
Transl Androl Urol, 6 (2017) 131-133
Abstract

FTY720 (Fingolimod) inhibits HIF-1 and HIF-2 signaling, promotes vascular remodeling and chemosensitizes in renal cell carcinoma animal model
Gstalder C, Ader I, Cuvillier O
Mol Cancer Ther, 15 (2016) 2565-2574
Abstract

Whole-exome sequencing in osteosarcoma reveals important heterogeneity of genetic alterations
Bousquet M, Noirot C, Accadbled F, Sales de Gauzy J, Castex MP, Brousset P, Gomez-Bouchet A
Ann Oncol, 27 (2016) 738-744

Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2a expression and activity in cancer
Bouquerel P, Gstalder C, Muller D, Laurent J, Brizuela L, Sabbadini RA, Malavaud B, Pyronnet S, Martineau Y, Ader I, Cuvillier O
Oncogenesis, 5 (2016) e209
Abstract

Voiding dysfunction in mice with experimental autoimmune encephalomyelitis: a multiple sclerosis-like disease
Even L, Bouali O, Roumiguié M, Cuvillier O, Malavaud B, Game X
World J Nephron Urol, 5 (2016) 4-10

Mechanisms of castration resistance : intratumoral hypoxia stimulates the androgen receptor expression
Linardi P, Brizuela L, Beauval JB, Roumiguié M, Soulié M, Cuvillier O, Malavaud B
Prog Urol, 26 (2016) 159-167
Abstract

Sphingomab, un anticorps anti-sphingosine 1-phosphate, comme agent anti-hypoxique dans le cancer
Cuvillier O
Médecine/Sciences, 31 (2015) 20-23
Abstract

Neutralizing S1P inhibits intratumoral hypoxia, induces vascular remodeling and sensitizes to chemotherapy in prostate cancer
Ader I, Bouquerel P, Gstalder C, Golzio M, Andrieu G, Zalvidea S, Richard S, Malavaud B, Sabbadini RA, Cuvillier O
Oncotarget, 6 (2015) 13803-13821
Abstract

Inhibition of Rac1-GTPase mediates the anti-migratory effects of metformin in prostate cancer cells
Dirat B, Ader I, Golzio M, Massa F, Mettouchi A, Laurent K, Larbret F, Malavaud B, Cormont M, Lemichez E, Cuvillier O, Tanti JF, Bost F
Mol Cancer Ther, 14 (2015) 586-596
Abstract

Gem GTPase acts upstream Gmip/RhoA and regulates actin remodeling and spindle positioning in early mitosis
Andrieu G, Quaranta M, Leprince C, Cuvillier O, Hatzoglou A
Carcinogenesis, 35 (2014) 2503-2511

Synthesis, structures, and anticancer activities of gold (I) complexes involving N-heterocyclic carbene ligands
Boselli L, Ader I, Carraz M, Hemmert C*, Cuvillier O*, Gornitzka H*
Eur J Med Chem, 85 (2014) 87-94

Synthesis of fluorinated agonist of sphingosine 1-phosphate receptor 1
Aliouane L, Chao S, Brizuela L, Pfund E, Cuvillier O, Jean L, Renard PY, Lequeux T
Bioorg Med Chem, 22 (2014) 4955-4960

La sphingosine 1-phosphate comme biomarqueur de la maladie d'Alzheimer
Ceccom J, Delisle MB, Cuvillier O
Médecine/Sciences, 30 (2014) 493-495

Osteoblast-derived sphingosine 1-phosphate to induce proliferation and confer resistance to therapeutics to bone metastasis-derived prostate cancer cells
Brizuela L, Martin C, Jeannot P, Ader I, Gstalder C, Andrieu G, Bocquet M, Laffosse JM, Gomez-Brouchet A, Malavaud B, Sabbadini RS, Cuvillier O
Mol Oncol, 8 (2014) 1181-1195

Sphingosine 1-phosphate and hypoxia signaling
Cuvillier O
in Molecular Mechanisms of Angiogenesis : from ontogenesis to oncogenesis, (Feige JJ, Pagès G and Soncin F, Eds.), Springer (2014) 199-217

Reduced sphingosine kinase-1 and enhanced sphingosine 1-posphate lyase expression demonstrate deregulated sphingosine 1-phosphate signaling in Alzheimer's disease
Ceccom J, Loukh N, Lauwers-Cances V, Touriol C, Nicaise Y, Gentil C, Uro-Coste E, Pitson S, Maurage CA, Duyckaerts C, Cuvillier O*, Delisle MB*
Acta Neuropathologica Comm, 2 (2014) 12

Polyphenols in prostate cancer
Brizuela L, Cuvillier O
in 'Polyphenols in health and disease', Academic Press, Vol 1 (2014) 1217-1230

Hypoxia, therapeutic resistance and sphingosine 1-phosphate
Cuvillier O, Ader I, Bouquerel P, Brizuela L, Gstalder C, Malavaud B
in 'Advances in Cancer Research, The role of sphingolipids in cancer development and therapy', Elsevier, Vol 117 (2013) 117-141

First evidence of sphingosine 1-phosphate lyase protein expression and activity in human neoplasm. Implication for resistance to therapeutics in prostate cancer
Brizuela L, Ader I, Mazerolles C, Bocquet M, Malavaud B, Cuvillier O
Mol. Cancer Ther, 11 (2012) 1841-1851

Les récepteurs à sphingosine 1-phosphate : de la biologie à la physio(patho)logie
Cuvillier O
Médecine/Sciences, 28 (2012) 953-959

La voie sphingosine kinase-1/sphingosine 1-phosphate dans l'hypoxie tumorale
Cuvillier O
VEGF Actu, 26 (2012) 6-8

Biochemical methods for quantifying sphingolipids : ceramide, sphingosine, sphingosine kinase-1 activity and sphingosine 1-phosphate
Brizuela L, Cuvillier O
in ‘Methods in Molecular Biology, S1P signaling Methods and Protocols’, Springer Science vol 874 (2012), 1-20

Biomarkers of aggressiveness in prostate cancer
Cuvillier O, Malavaud B
in ‘Prostate Cancer -Diagnosis and Therapeutic Advances', Intech Press (2011) 3-20

Hypoxia Inducible Factors and sphingosine 1-phosphate signaling
Cuvillier O, Ader I
Anticancer Agents Med Chem, 11 (2011) 854-862

Increased sphingosine kinase-1 expression and activity in prostate cancer resection specimens
Malavaud B, Pchejetski D, Mazerolles C, Russano de Paiva Silva G, Doumerc N, Calvet C, Pitson S, Rischmann P, Cuvillier O
Eur J. Cancer, 46 (2010) 3417-3424

FTY720 (Fingolimod) sensitizes prostate cancer cells to radiotherapy by inhibition of sphingosine kinase-1
Pchejetski D, Brizuela L, Sauer L, Doumerc N, Golzio M, Salunkhe V, Teissié J, Malavaud B, Waxman J, Cuvillier O
Cancer Res., 70 (2010) 8651-8661

The sphingosine kinase-1 survival pathway : a potential target for tumor-suppressive tea and wine polyphenols in prostate cancer
Brizuela L, Dayon A, Doumerc N, Ader I, Golzio M, Izard JC, Hara Y, Malavaud B, Cuvillier O
Faseb J, 24 (2010) 3882-3894

Activation of sphingosine kinase-1 in cancer: implications for therapeutic targeting
Cuvillier O, Ader I, Bouquerel P, Brizuela L, Malavaud B, Mazerolles C, Rischmann P
Curr Mol Pharmacol, 3 (2010) 53-65

Sphingosine kinase-1 is a mediator of androgen-induced osteoblast cell growth
Martin C, Laffosse JM, Malavaud B, Cuvillier O
Biochem Biophys Res Comm, 391 (2010) 669-673

Sphingosine kinase inhibition sensitizes to hormone-resistant prostate cancer cells to docetaxel
Sauer L, Nunes J, Salunkhe V, Skalska L, Kohama T, Cuvillier O, Waxman J, Pchejetski D
Int J Cancer, 125 (2009) 2728-2736

Sphingosine kinase-1 is central to androgen-regulated prostate cancer growth and survival
Dayon A, Brizuela L, Martin C, Mazerolles C, Pirot N, Doumerc N, Nogueira L, Golzio M, Teissié J, Serre G, Rischmann P, Malavaud B, Cuvillier O
PLoS One, 4 (2009) e8048

When the sphingosine kinase-1/sphingosine 1-phosphate pathway meets hypoxia signaling: new targets for cancer therapy
Ader I, Malavaud B, Cuvillier O
Cancer Res, 69 (2009) 3723-3726

Targeting the sphingolipid metabolism to sensitize pancreatic cancer cell to gemcitabine
Guillermet J*, Davesne L*, Pchejetski D*, Saint-Laurent N, Brizuela L, Guilbeau-Frugier C, Delisle MB, Cuvillier O, Susini C, Bousquet C
Mol Cancer Ther, 8 (2009) 809-820

Chemosensitizing effect of sphingosine kinase-1 inhibition in prostate cancer cell and animal models
Pchejetski D, Doumerc N, Golzio M, Naymark M, Teissié J, Kohama T, Waxman J, Malavaud B, Cuvillier O
Mol Cancer Ther, 7 (2008) 1836-1845

Downregulating sphingosine kinase-1 for cancer therapy
Cuvillier O
Expert Opin Ther Targets, 12 (2008) 1009-1020

Sphingosine kinase-1 : a new modulator of HIF-1 during hypoxia in human cancer cells
Ader I, Brizuela L, Bouquerel P, Malavaud B, Cuvillier O
Cancer Res, 68 (2008) 8635-8642

Sphingosine kinase-1 is a downstream regulator of imatinib-induced apoptosis in chronic myeloid leukemia cells
Bonhoure E, Lauret A, Barnes DJ, Martin C, Malavaud B, Kohama T, Melo JV, Cuvillier O
Leukemia, 22 (2008) 971-979

Critical role for sphingosine kinase-1 in regulating survival of amyloid- peptide-treated neuroblastoma SH-SY5Y cells
Gomez-Brouchet A, Pchejetski D, Brizuela L, Garcia V, Altié MF, Maddelein ML, Delisle MB, Cuvillier O
Mol Pharmacol, 72 (2007) 341-349

Sphingosine kinase-1: a potential therapeutic target in cancer
Cuvillier O
Anticancer Drugs, 18 (2007) 105-110

Oxidative stress-dependent sphingosine kinase-1 inhibition mediates myocardiac cell apoptosis induced by MAO-A
Pchejetski D, Kundozova O, Dayon A, Calisse D, Seif I, Parini A, Cuvillier O
Circ Res, 100 (2007) 41-49
See comment : Circ. Res., 100 (2007) 7-9

Regulation by sphingosine 1-phosphate of Bax and Bad activities during apoptosis in a MEK1/2-dependent manner
Betito S, Cuvillier O
Biochem Biophys Res Comm, 341 (2006) 1273-1277

Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting sphingosine kinase-1
Bonhoure E, Pchejetski D, Aouali N, Levade T, Morjani H, Kohama T, Cuvillier O
Leukemia, 20 (2006) 95-102

Sphingosine kinase-1 as a sensor to chemotherapy in prostate adenocarcinoma cell and mouse models
Pchejetski D, Golzio M, Bonhoure E, Calvet C, Doumerc N, Garcia V, Mazerolles C, Rischmann P, Teissié J, Malavaud B, Cuvillier O
Cancer Res, 65 (2005) 11667-11675





LAB MEMBERS





Permanent staff at IPBS


Olivier Cuvillier, PhD
Director of Research from the French National Institute of Health and Medical Research (INSERM)
Email :
olivier.cuvillier@ipbs.fr





Marie-Lise Maddelein, PhD
Senior Scientist from the French National Center for Scientific Research (CNRS)
Email :
marie-lise.maddelein@ipbs.fr


Franck Talmont, PhD
Engineer from the French National Center for Scientific Research (CNRS)
Email :
franck.talmont@ipbs.fr


Anastassia Hatzoglou, PhD
Full Professor from the University of Toulouse (UPS)
Email :
anastassia.hatzoglou@ipbs.fr

Non Permanent staff at IPBS


Arrate Lopez de Abesraturi, PhD
Postdoctoral Fellow, IMODI


Gaëlle Dominguez, PhD
Postdoctoral Fellow, France Alzheimer (collab. CHU Toulouse)


Celia Martron
Technician, POCTEFA


Amélie Chorfa
M2R student, Toulouse


Anouar Haroun
M2R student, Limoges




Permanent staff at Oncopôle


Bernard Malavaud, MD, PhD
Urologist from the Institut Universitaire du Cancer Oncopôle (IUC) and Professor from the University of Toulouse
Email :
malavaud.bernard@iuct-oncopole.fr


Anne Gomez-Brouchet, MD, PhD
Pathologist from the Institut Universitaire du Cancer Oncopôle (IUC) and Professor from the University of Toulouse
Email :
brouchet.anne@iuct-oncopole.fr



CURRENT FINANCIAL SUPPORT




Interreg POCTEFA
Our Lab is a partner of the PIREPRED consortium funded by POCTEFA action
Cofinanciado por el Fondo Europe de Desarrollo Regional (FEDER)
Cofinancé par le Fonds Européen de Développement Régional (FEDER).



Stacks Image 338



Région Occitanie
Our Lab is the partner of the Institut National Polytechnique de Toulouse


Stacks Image 347



Investissements d’Avenir : Projets Structurants des Pôles de Compétitivité (BPI)
Our Lab is part of the ‘IMODI’ consortium

Read more





Stacks Image 358





PAST FINANCIAL SUPPORT

Stacks Image 499





ONCO-UROLOGY BLOG




Lorem ipsum dolor sit amet, sapien platea morbi dolor lacus nunc, nunc ullamcorper. Felis aliquet egestas vitae, nibh ante quis quis dolor sed mauris. Erat lectus sem ut lobortis, adipiscing ligula eleifend, sodales fringilla mattis dui nullam. Ac massa aliquet.