Prostate Cancer (PCa) is one of the leading causes of death by cancer in men. In the recent years, it has dramatically increased, most likely due to clinical advances in the early diagnosis and possibly to increasing exposures to environmental pollutants.
The large majority of PCa-related deaths are attributable to advanced, metastatic forms of the disease rather than to localized PCa. During the past six years, we have focused our research on defining molecules able to interfere with the energy metabolism of cancer cells.
We have successfully characterized anti-tumoral actions of several energy disruptors, specifically metformin which targets mitochondrial metabolism and function. A growing body of evidence suggests that mitochondria play a key role in cancer not only in the initiating stages but also in the progression of the disease to the aggressive forms. However, the metabolic modifications underlying PCa metastatic spread are poorly known.
In this context, our program will focus on two main axis:
1) Investigating the metabolic modifications induced by metformin and deciphering the metabolic changes associated with the formation of metastasis in prostate cancer cells.
2) Determining how Environmental Disrupting Chemicals (EDCs) modify cellular and mitochondrial metabolism in relation with PCa progression/aggressiveness.
Sirtuin 7: a new marker of aggressiveness in prostate cancer
Haider R, Massa F, Kaminski L, Clavel S, Djabari Z, Robert G, Laurent K, Michiels JF, Durand M, Ricci JE, Tanti JF, Bost F, Ambrosetti D
Oncotarget 2017 Sep;8(44):77309-77316 PMID : 29100388
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells
Loubiere C, Clavel S, Gilleron J, Harisseh R, Fauconnier J, Ben-Sahra I, Kaminski L, Laurent K, Herkenne S, Lacas-Gervais S, Ambrosetti D, Alcor D, Rocchi S, Cormont M, Michiels JF, Mari B, Mazure NM, Scorrano L, Lacampagne A, Gharib A, Tanti JF, Bost F
Sci Rep 2017 Jul;7(1):5040 PMID : 28698627
Energy disruptors: rising stars in anticancer therapy?
Bost F, Decoux-Poullot AG, Tanti JF, Clavel S
Oncogenesis 2016;5:e188 PMID : 26779810
Inhibition of the GTPase Rac1 mediates the antimigratory 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. 2015 Feb;14(2):586-96 PMID : 25527635
Metformin-induced energy deficiency leads to the inhibition of lipogenesis in prostate cancer cells
Loubière C, Goiran T, Laurent K, Djabari Z, Tanti JF, Bost F
Oncotarget 2015 Jun;6(17):15652-61 PMID : 26002551
Cord blood insulin-like peptide 3 (INSL3) but not testosterone is reduced in idiopathic cryptorchidism
Fénichel P, Lahlou N, Coquillard P, Panaïa-Ferrari P, Wagner-Mahler K, Brucker-Davis F
Clin. Endocrinol. (Oxf) 2015 Feb;82(2):242-7 PMID : 24826892
A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development
Chevalier N, Brucker-Davis F, Lahlou N, Coquillard P, Pugeat M, Pacini P, Panaïa-Ferrari P, Wagner-Mahler K, Fénichel P
Hum. Reprod. 2015 Feb;30(2):447-53 PMID : 25527819
Endocrine disruptors: new players in the pathophysiology of type 2 diabetes?
Chevalier N, Fénichel P
Diabetes Metab. 2015 Apr;41(2):107-15 PMID : 25454091
Increased gene copy number of VAMP7 disrupts human male urogenital development through altered estrogen action
Tannour-Louet M, Han S, Louet JF, Zhang B, Romero K, Addai J, Sahin A, Cheung SW, Lamb DJ
Nat. Med. 2014 Jul;20(7):715-24 PMID : 24880616
Genetic variants of GPER/GPR30, a novel estrogen-related G protein receptor, are associated with human seminoma
Chevalier N, Paul-Bellon R, Camparo P, Michiels JF, Chevallier D, Fénichel P
Int J Mol Sci 2014;15(1):1574-89 PMID : 24451139