Funders
Research
The team aims to identify the molecular mechanisms involved in the differentiation and maintenance of homeostasis of endocrine tissues and to understand how deregulation of these mechanisms leads to the development of pathologies. Our activity is currently divided into three axes that are strongly interconnected in terms of the cellular and molecular mechanisms studied and the scientific approaches used
- Mechanisms of adrenal cortex differentiation
- Mecanisms of adrenocortical tumorigenesis
We are trying to understand the molecular mechanisms involved in the initiation and progression of adrenocortical cancer (adrenocortical carcinoma). Our approach is based on genetically modified mouse models that reproduce alterations in signaling pathways altered in patients. These models allow a better understanding of tumorigenesis processes and constitute excellent pre-clinical tools allowing the evaluation of innovative therapeutic approaches. In this context our projects currently aim to understand the anti-tumor effects of testosterone and to identify new levers making it possible to mobilize anti-tumor immune activity in the context of adrenocortical carcinoma.
- Mechanisms of gonadal differentiation and plasticity control
- Techniques used in the team
-Genetically modified mouse models to assess the role of alterations in pathophysiological processes
-Histological and immunohistochemical analyzes
-Integrative multi-omics analyzes
-Spectral flow cytometry
-Chromatin immunoprecipitation (ChIPseq)
Members
Publications
Loss of SUMO-specific protease 2 causes isolated glucocorticoid deficiency by blocking adrenal cortex zonal transdifferentiation in mice.
Published on 21 Dec 2022 in Nature communications , vol. 13 - pp 7858
Dufour D , Dumontet T , Sahut-Barnola I, Carusi A, Onzon M , Pussard E, Wilmouth JJ , Olabe J , Lucas C , Levasseur A , Damon-Soubeyrand C , Pointud JC , Roucher-Boulez F , Tauveron I , Bossis G, Yeh ET, Breault DT, Val P , Lefrançois-Martinez AM, Martinez A
Loss of LGR4/GPR48 causes severe neonatal salt-wasting due to disrupted WNT signaling altering adrenal zonation.
Published on 20 Dec 2022 in The Journal of clinical investigation
Lucas C , Sauter KS, Steigert M, Mallet D, Wilmouth J Jr , Olabe J , Plotton I, Morel Y, Aeberli D, Wagner F, Clevers H, Pandey AV, Val P , Roucher-Boulez F , Fluck CE
Steroidogenic Factor-1 Lineage Origin of Skin Lesions in Carney Complex Syndrome.
Published on 12 Nov 2022 in The Journal of investigative dermatology , vol. 142 - pp 2949-2957.e9
Sahut-Barnola I , Lefrançois-Martinez AM , Dufour D , Botto JM, Kamilaris C, Faucz FR, Stratakis CA, Val P , Martinez A
Sexually dimorphic activation of innate antitumor immunity prevents adrenocortical carcinoma development.
Published on 14 Oct 2022 in Science advances , vol. 8 - pp eadd0422
Wilmouth JJ Jr , Olabe J , Garcia-Garcia D , Lucas C , Guiton R , Roucher-Boulez F , Dufour D , Damon-Soubeyrand C , Sahut-Barnola I , Pointud JC , Renaud Y , Levasseur A , Tauveron I , Lefrançois-Martinez AM , Martinez A , Val P
β-Catenin activation and illicit receptor expression in adrenocortical cells.
Published on 07 Feb 2022 in Endocrine-related cancer , vol. 29 - pp 151-162
Le Mestre J, Thomas M, Duparc C, Val P , Bures C, Tuech JJ, Sabourin JC, Baert-Desurmont S, Lefebvre H, Louiset E
Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.
Published on 01 Dec 2021 in The Journal of clinical investigation , vol. 131
Djari C , Sahut-Barnola I , Septier A , Plotton I, Montanier N , Dufour D , Levasseur A , Wilmouth J Jr , Pointud JC , Faucz FR, Kamilaris C, Lopez AG, Guillou F, Swain A, Vainio SJ, Tauveron I , Val P , Lefebvre H, Stratakis CA, Martinez A , Lefrançois-Martinez AM
How can we minimise the use of regular oral corticosteroids in asthma?
Published on 31 Mar 2020 in European respiratory review : an official journal of the European Respiratory Society , vol. 29
Bourdin A, Adcock I, Berger P, Bonniaud P, Chanson P, Chenivesse C, de Blic J, Deschildre A, Devillier P, Devouassoux G, Didier A, Garcia G, Magnan A, Martinat Y, Perez T, Roche N, Taillé C, Val P , Chanez P
Hormonal and spatial control of SUMOylation in the human and mouse adrenal cortex.
Published on 12 Sep 2019 in FASEB journal : official publication of the Federation of American Societies for Experimental Biology , vol. 33 - pp 10218-10230
Dumontet T , Sahut-Barnola I , Dufour D , Lefrançois-Martinez AM , Berthon A , Montanier N , Ragazzon B, Djari C , Pointud JC , Roucher-Boulez F , Batisse-Lignier M , Tauveron I , Bertherat J, Val P , Martinez A
EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness.
Published on 30 Aug 2019 in British journal of cancer , vol. 121 - pp 384-394
Tabbal H , Septier A , Mathieu M , Drelon C , Rodriguez S , Djari C , Batisse-Lignier M , Tauveron I , Pointud JC , Sahut-Barnola I , Ragazzon B, Assié G, Bertherat J, Lefrançois-Martinez AM , Martinez A , Val P
A ZNRF3-dependent Wnt/β-catenin signaling gradient is required for adrenal homeostasis.
Published on 01 Feb 2019 in Genes & development , vol. 33 - pp 209-220
Basham KJ, Rodriguez S , Turcu AF, Lerario AM, Logan CY, Rysztak MR, Gomez-Sanchez CE, Breault DT, Koo BK, Clevers H, Nusse R, Val P , Hammer GD
Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex.
Published on 26 Dec 2018 in Proceedings of the National Academy of Sciences of the United States of America , vol. 115 - pp E12265-E12274
Mathieu M , Drelon C , Rodriguez S , Tabbal H , Septier A , Damon-Soubeyrand C , Dumontet T , Berthon A , Sahut-Barnola I , Djari C , Batisse-Lignier M , Pointud JC , Richard D, Kerdivel G, Calméjane MA, Boeva V, Tauveron I , Lefrançois-Martinez AM , Martinez A , Val P
PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal.
Published on 25 Jan 2018 in JCI insight , vol. 3
Dumontet T , Sahut-Barnola I , Septier A , Montanier N , Plotton I, Roucher-Boulez F , Ducros V, Lefrançois-Martinez AM , Pointud JC , Zubair M, Morohashi KI, Breault DT, Val P , Martinez A
P53/Rb inhibition induces metastatic adrenocortical carcinomas in a preclinical transgenic model.
Published on 30 Aug 2017 in Oncogene , vol. 36 - pp 4445-4456
Batisse-Lignier M , Sahut-Barnola I , Tissier F, Dumontet T , Mathieu M , Drelon C , Pointud JC , Damon-Soubeyrand C , Marceau G , Kemeny JL, Bertherat J, Tauveron I , Val P , Martinez A , Lefrançois-Martinez AM
PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease.
Published on 22 Sep 2016 in JCI insight , vol. 1 - pp e87958
Bram Z, Louiset E, Ragazzon B, Renouf S, Wils J, Duparc C, Boutelet I, Rizk-Rabin M, Libé R, Young J, Carson D, Vantyghem MC, Szarek E, Martinez A , Stratakis CA, Bertherat J, Lefebvre H
PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development.
Published on 14 Sep 2016 in Nature communications , vol. 7 - pp 12751
Drelon C , Berthon A , Sahut-Barnola I , Mathieu M , Dumontet T , Rodriguez S , Batisse-Lignier M , Tabbal H , Tauveron I , Lefrançois-Martinez AM , Pointud JC , Gomez-Sanchez CE, Vainio S, Shan J, Sacco S, Schedl A, Stratakis CA, Martinez A , Val P
Mouse Models Recapitulating Human Adrenocortical Tumors: What Is Lacking?
Published on 15 Jul 2016 in Frontiers in endocrinology , vol. 7 - pp 93
Leccia F , Batisse-Lignier M , Sahut-Barnola I , Val P , Lefrançois-Martinez AM , Martinez A
EZH2 is overexpressed in adrenocortical carcinoma and is associated with disease progression.
Published on 01 Jul 2016 in Human molecular genetics , vol. 25 - pp 2789-2800
Drelon C, Berthon A, Mathieu M, Ragazzon B, Kuick R, Tabbal H, Septier A, Rodriguez S, Batisse-Lignier M, Sahut-Barnola I, Dumontet T, Pointud JC, Lefrançois-Martinez AM, Baron S , Giordano TJ, Bertherat J, Martinez A, Val P
The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.
Published on 15 Jun 2016 in Genes & development , vol. 30 - pp 1389-94
Vidal V, Sacco S, Rocha AS, da Silva F, Panzolini C, Dumontet T , Doan TM, Shan J, Rak-Raszewska A, Bird T, Vainio S, Martinez A , Schedl A
Editorial: Adrenal Cortex: From Physiology to Disease.
Published on 01 Jun 2016 in Frontiers in endocrinology , vol. 7 - pp 51
Pregnancy, Primary Aldosteronism, and Somatic CTNNB1 Mutations.
Published on 14 Apr 2016 in The New England journal of medicine , vol. 374 - pp 1493-4
Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma.
Published on 27 Jul 2015 in Oncogenesis , vol. 4 - pp e161
Lefèvre L, Omeiri H, Drougat L, Hantel C, Giraud M, Val P , Rodriguez S , Perlemoine K, Blugeon C, Beuschlein F, de Reyniès A, Rizk-Rabin M, Bertherat J, Ragazzon B
Adrenal cortex tissue homeostasis and zonation: A WNT perspective.
Published on 15 Jun 2015 in Molecular and cellular endocrinology , vol. 408 - pp 156-64
Drelon C , Berthon A , Mathieu M , Martinez A , Val P
Aldose reductases influence prostaglandin F2α levels and adipocyte differentiation in male mouse and human species.
Published on 12 May 2015 in Endocrinology , vol. 156 - pp 1671-84
Pastel E , Pointud JC , Loubeau G , Dani C, Slim K, Martin G, Volat F, Sahut-Barnola I , Val P , Martinez A , Lefrançois-Martinez AM
mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD).
Published on 15 Oct 2014 in Human molecular genetics , vol. 23 - pp 5418-28
de Joussineau C , Sahut-Barnola I , Tissier F, Dumontet T , Drelon C , Batisse-Lignier M , Tauveron I , Pointud JC , Lefrançois-Martinez AM , Stratakis CA, Bertherat J, Val P , Martinez A
Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial.
Published on 12 Jul 2014 in Reproductive biology and endocrinology : RB&E , vol. 12 - pp 65
Pons-Rejraji H , Brugnon F , Sion B, Maqdasy S , Gouby G, Pereira B, Marceau G , Gremeau AS, Drevet J , Grizard G, Janny L , Tauveron I
WNT/β-catenin signalling is activated in aldosterone-producing adenomas and controls aldosterone production.
Published on 15 Feb 2014 in Human molecular genetics , vol. 23 - pp 889-905
Berthon A , Drelon C , Ragazzon B, Boulkroun S, Tissier F, Amar L, Samson-Couterie B, Zennaro MC, Plouin PF, Skah S, Plateroti M, Lefèbvre H, Sahut-Barnola I , Batisse-Lignier M , Assié G, Lefrançois-Martinez AM , Bertherat J, Martinez A , Val P
WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP-like progenitors within the adrenal gland.
Published on 14 Oct 2013 in Developmental cell , vol. 27 - pp 5-18
Bandiera R, Vidal VP, Motamedi FJ, Clarkson M, Sahut-Barnola I , von Gise A, Pu WT, Hohenstein P, Martinez A , Schedl A
Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation.
Published on 03 Sep 2013 in Proceedings of the National Academy of Sciences of the United States of America , vol. 110 - pp 14801-6
Kanczkowski W, Alexaki VI, Tran N, Großklaus S, Zacharowski K, Martinez A , Popovics P, Block NL, Chavakis T, Schally AV, Bornstein SR
Adrenocortical cancer and IGF2: is the game over or our experimental models limited?
Published on 12 Feb 2013 in The Journal of clinical endocrinology and metabolism , vol. 98 - pp 505-7
In vivo evidence for the crucial role of SF1 in steroid-producing cells of the testis, ovary and adrenal gland.
Published on 12 Dec 2012 in Development (Cambridge, England) , vol. 139 - pp 4561-70
Buaas FW, Gardiner JR, Clayton S, Val P , Swain A
Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.
Published on 30 Nov 2012 in Diabetes , vol. 61 - pp 2796-806
Volat FE, Pointud JC , Pastel E , Morio B, Sion B, Hamard G, Guichardant M, Colas R, Lefrançois-Martinez AM , Martinez A
Analysis of the role of Igf2 in adrenal tumour development in transgenic mouse models.
Published on 28 Aug 2012 in PloS one , vol. 7 - pp e44171
Drelon C , Berthon A , Ragazzon B, Tissier F, Bandiera R, Sahut-Barnola I, de Joussineau C , Batisse-Lignier M , Lefrançois-Martinez AM, Bertherat J, Martinez A , Val P
Aldo-Keto Reductases 1B in Endocrinology and Metabolism.
Published on 02 Aug 2012 in Frontiers in pharmacology , vol. 3 - pp 148
Pastel E , Pointud JC , Volat F, Martinez A , Lefrançois-Martinez AM
Wnt/β-catenin signalling in adrenal physiology and tumour development.
Published on 31 Mar 2012 in Molecular and cellular endocrinology , vol. 351 - pp 87-95
Berthon A , Martinez A , Bertherat J, Val P
The cAMP pathway and the control of adrenocortical development and growth.
Published on 31 Mar 2012 in Molecular and cellular endocrinology , vol. 351 - pp 28-36
de Joussineau C , Sahut-Barnola I , Levy I, Saloustros E, Val P , Stratakis CA, Martinez A
Identification, cloning and regulation of cDNA encoding aldo-keto reductase 1B7 in the adrenal gland of two Saharan rodents Meriones libycus (Libyan jird) and Gerbillus gerbillus (gerbil).
Published on 01 Dec 2011 in General and comparative endocrinology , vol. 174 - pp 292-300
Mataoui-Mazari H, Amirat Z, Khammar F, Martinez A
Transcriptional control of adrenal steroidogenesis: novel connection between Janus kinase (JAK) 2 protein and protein kinase A (PKA) through stabilization of cAMP response element-binding protein (CREB) transcription factor.
Published on 23 Sep 2011 in The Journal of biological chemistry , vol. 286 - pp 32976-85
Lefrancois-Martinez AM , Blondet-Trichard A, Binart N, Val P , Chambon C, Sahut-Barnola I , Pointud JC , Martinez A
Gene dosage effects and transcriptional regulation of early mammalian adrenal cortex development.
Published on 08 Jul 2010 in Molecular and cellular endocrinology , vol. 323 - pp 105-14
Val P , Swain A
Cushing’s syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.
Published on 10 Jun 2010 in PLoS genetics , vol. 6 - pp e1000980
Sahut-Barnola I , de Joussineau C , Val P , Lambert-Langlais S, Damon C, Lefrançois-Martinez AM, Pointud JC , Marceau G , Sapin V , Tissier F, Ragazzon B, Bertherat J, Kirschner LS, Stratakis CA, Martinez A
Constitutive beta-catenin activation induces adrenal hyperplasia and promotes adrenal cancer development.
Published on 15 Apr 2010 in Human molecular genetics , vol. 19 - pp 1561-76
Berthon A , Sahut-Barnola I , Lambert-Langlais S, de Joussineau C , Damon-Soubeyrand C , Louiset E, Taketo MM, Tissier F, Bertherat J, Lefrançois-Martinez AM, Martinez A , Val P
Pasture-feeding of Charolais steers influences skeletal muscle metabolism and gene expression.
Published on 30 Oct 2009 in Journal of physiology and pharmacology : an official journal of the Polish Physiological Society , vol. 60 Suppl 3 - pp 83-90
Cassar-Malek I, Jurie C, Bernard C, Barnola I , Micol D, Hocquette JF
Aldo keto reductase 1B7 and prostaglandin F2alpha are regulators of adrenal endocrine functions.
Published on 07 Oct 2009 in PloS one , vol. 4 - pp e7309
Lambert-Langlais S, Pointud JC , Lefrançois-Martinez AM , Volat F, Manin M, Coudoré F, Val P , Sahut-Barnola I , Ragazzon B, Louiset E, Delarue C, Lefebvre H, Urade Y, Martinez A
24-dehydrocholesterol reductase/seladin-1: a key protein differentially involved in adrenocorticotropin effects observed in human and rat adrenal cortex.
Published on 30 Sep 2009 in Endocrinology , vol. 150 - pp 4180-90
Battista MC, Roberge C, Martinez A , Gallo-Payet N
Inactivation of the Carney complex gene 1 (protein kinase A regulatory subunit 1A) inhibits SMAD3 expression and TGF beta-stimulated apoptosis in adrenocortical cells.
Published on 15 Sep 2009 in Cancer research , vol. 69 - pp 7278-84
Ragazzon B, Cazabat L, Rizk-Rabin M, Assie G, Groussin L, Fierrard H, Perlemoine K, Martinez A , Bertherat J
The transcription co-factor CITED2 functions during sex determination and early gonad development.
Published on 15 Aug 2009 in Human molecular genetics , vol. 18 - pp 2989-3001
Buaas FW, Val P , Swain A
Mouse model for bilateral adrenal hyperplasia.
Published on 30 Jun 2009 in Annales d'endocrinologie , vol. 70 - pp 194
Sahut-Barnola I , De Joussineau C , Val P , Lambert-Langlais S, Lefrançois-Martinez AM , Pointud JC , Marceau G , Sapin V , Ragazzon B, Bertherat J, Kirschner LS, Stratakis CA, Martinez A
A transgenic mouse line with specific Cre recombinase expression in the adrenal cortex.
Published on 05 Mar 2009 in Molecular and cellular endocrinology , vol. 300 - pp 197-204
Lambert-Langlais S, Val P , Guyot S, Ragazzon B, Sahut-Barnola I , De Haze A , Lefrançois-Martinez AM , Martinez A
Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.
Published on 02 Mar 2009 in Journal of biochemistry , vol. 145 - pp 161-8
Kabututu Z, Manin M, Pointud JC , Maruyama T, Nagata N, Lambert S , Lefrançois-Martinez AM, Martinez A , Urade Y
Oryza Tag Line, a phenotypic mutant database for the Genoplante rice insertion line library.
Published on 30 Jan 2008 in Nucleic acids research , vol. 36 - pp D1022-7
Larmande P, Gay C, Lorieux M, Périn C, Bouniol M, Droc G, Sallaud C, Perez P, Barnola I , Biderre-Petit C, Martin J, Morel JB, Johnson AA, Bourgis F, Ghesquière A, Ruiz M, Courtois B, Guiderdoni E
