The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

被引：175

作者：

Torrano, Veronica ^{[1
]}

Valcarcel-Jimenez, Lorea ^{[1
]}

Rosa Cortazar, Ana ^{[1
]}

Liu, Xiaojing ^{[2
]}

Urosevic, Jelena ^{[3
]}

Castillo-Martin, Mireia ^{[4
,5
]}

Fernandez-Ruiz, Sonia ^{[1
]}

Morciano, Giampaolo ^{[6
]}

Caro-Maldonado, Alfredo ^{[1
]}

Guiu, Marc ^{[3
]}

Zuniga-Garcia, Patricia ^{[1
]}

Graupera, Mariona ^{[7
]}

Bellmunt, Anna ^{[3
]}

Pandya, Pahini ^{[8
]}

Lorente, Mar ^{[9
,10
]}

Martin-Martin, Natalia ^{[1
]}

David Sutherland, James ^{[1
]}

Sanchez-Mosquera, Pilar ^{[1
]}

Bozal-Basterra, Laura ^{[1
]}

Zabala-Letona, Amaia ^{[1
]}

Arruabarrena-Aristorena, Amaia ^{[1
]}

Berenguer, Antonio ^{[11
]}

Embade, Nieves ^{[1
]}

Ugalde-Olano, Aitziber ^{[12
]}

Lacasa-Viscasillas, Isabel ^{[13
]}

Loizaga-Iriarte, Ana ^{[13
]}

Unda-Urzaiz, Miguel ^{[13
]}

Schultz, Nikolaus ^{[14
]}

Maria Aransay, Ana ^{[1
,15
]}

Sanz-Moreno, Victoria ^{[8
]}

Barrio, Rosa ^{[1
]}

Velasco, Guillermo ^{[9
,10
]}

Pinton, Paolo ^{[6
]}

Cordon-Cardo, Carlos ^{[4
]}

Locasale, Jason W. ^{[2
]}

Gomis, Roger R. ^{[3
,16
]}

Carracedo, Arkaitz ^{[1
,17
,18
]}

机构：

[1] CIC bioGUNE, Bizkaia Technol Pk,Bldg 801A, Derio 48160, Bizkaia, Spain

[2] Duke Univ, Sch Med, Duke Mol Physiol Inst, Dept Pharmacol & Canc Biol,Duke Canc Inst, Durham, NC 27710 USA

[3] Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Oncol Programme, Barcelona 08028, Catalonia, Spain

[4] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA

[5] Fundacao Champalimaud, Dept Pathol, P-1400038 Lisbon, Portugal

[6] Univ Ferrara, Sect Pathol Oncol & Expt Biol, Dept Morphol Surg & Expt Med, I-44100 Ferrara, Italy

[7] Inst Invest Biomed Bellvitge IDIBELL, Vasc Signalling Lab, Gran Via Hosp 199-203, Barcelona 08907, Spain

[8] Kings Coll London, Randall Div Cell & Mol Biophys, Tumour Plast Team, New Hunts House,Guys Campus, London SE1 1UL, England

[9] Univ Complutense, Sch Biol, Dept Biochem & Mol Biol 1, E-28040 Madrid, Spain

[10] Inst Invest Sanitarias San Carlos IdISSC, Madrid 28040, Spain

[11] IRB Barcelona, Biostat Bioinformat Uni, Parc Cient Barcelona, Barcelona 08028, Spain

[12] Basurto Univ Hosp, Dept Pathol, Bilbao 48013, Spain

[13] Basurto Univ Hosp, Dept Urol, Bilbao 48013, Spain

[14] Mem Sloan Kettering Canc Ctr, Computat Biol, New York, NY 10065 USA

[15] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona 08010, Spain

[16] ICREA, Barcelona 08010, Spain

[17] Ikerbasque, Basque Fdn Sci, E-48011 Bilbao, Spain

[18] Univ Basque Country UPV EHU, Dept Mol Biol & Biochem, POB 644, E-48080 Bilbao, Spain

来源：

NATURE CELL BIOLOGY | 2016年 / 18卷 / 06期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

HIGH-RESOLUTION METABOLOMICS; TRANSCRIPTIONAL COREGULATORS; OXIDATIVE-METABOLISM; PTEN; TUMOR; PGC-1-ALPHA; ACTIVATION; REGULATOR; RECEPTOR; ALPHA;

D O I：

10.1038/ncb3357

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1 alpha) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1 alpha is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1 alpha opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1 alpha activates an oestrogen-related receptor alpha (ERR alpha)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1 alpha-ERR alpha pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment.

引用

页码：645 / +

页数：23

共 69 条

[1]

[Anonymous], 2002, Experimental designs and data analysis for biologists

[2] Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma [J].

Arroyo-Berdugo, Yoana ;

Alonso, Santos ;

Ribas, Gloria ;

Ibarrola-Villava, Maider ;

Pena-Chilet, Maria ;

Martinez-Cadenas, Conrado ;

Gardeazabal, Jesus ;

Antonio Raton-Nieto, Juan ;

Sanchez-Diez, Ana ;

Maria Careaga, Jesus ;

Perez-Yarza, Gorka ;

Carretero, Gregorio ;

Martin-Gonzalez, Manuel ;

Gomez-Fernandez, Cristina ;

Nagore, Eduardo ;

Asumendi, Aintzane ;

Dolores Boyano, Maria .

PLOS ONE, 2014, 9 (04)

[3] The PGC-1α/ERRα Axis Represses One-Carbon Metabolism and Promotes Sensitivity to Anti-folate Therapy in Breast Cancer [J].

Audet-Walsh, Etienne ;

Papadopoli, David J. ;

Gravel, Simon-Pierre ;

Yee, Tracey ;

Bridon, Gaelle ;

Caron, Maxime ;

Bourque, Guillaume ;

Giguere, Vincent ;

St-Pierre, Julie .

CELL REPORTS, 2016, 14 (04) :920-931

[4] Different outcomes of the Wilcoxon-Mann-Whitney test from different statistics packages [J].

Bergmann, R ;

Ludbrook, J ;

Spooren, WPJM .

AMERICAN STATISTICIAN, 2000, 54 (01) :72-77

[5] Osteotropic cancers: From primary tumor to bone [J].

Buijs, Jeroen T. ;

van der Pluijm, Gabri .

CANCER LETTERS, 2009, 273 (02) :177-193

[6] Metabolic Reprogramming Is Required for Antibody Production That Is Suppressed in Anergic but Exaggerated in Chronically BAFF-Exposed B Cells [J].

Caro-Maldonado, Alfredo ;

Wang, Ruoning ;

Nichols, Amanda G. ;

Kuraoka, Masayuki ;

Milasta, Sandra ;

Sun, Lillian D. ;

Gavin, Amanda L. ;

Abel, E. Dale ;

Kelsoe, Garnett ;

Green, Douglas R. ;

Rathmell, Jeffrey C. .

JOURNAL OF IMMUNOLOGY, 2014, 192 (08) :3626-3636

[7]

Carracedo A, 2008, J CLIN INVEST, V118, P3065, DOI [10.1172/jCI34739, 10.1172/JCI34739]

[8] Cancer metabolism: fatty acid oxidation in the limelight [J].

Carracedo, Arkaitz ;

Cantley, Lewis C. ;

Pandolfi, Pier Paolo .

NATURE REVIEWS CANCER, 2013, 13 (04) :227-232

[9] A metabolic prosurvival role for PML in breast cancer [J].

Carracedo, Arkaitz ;

Weiss, Dror ;

Leliaert, Amy K. ;

Bhasin, Manoj ;

de Boer, Vincent C. J. ;

Laurent, Gaelle ;

Adams, Andrew C. ;

Sundvall, Maria ;

Song, Su Jung ;

Ito, Keisuke ;

Finley, Lydia S. ;

Egia, Ainara ;

Libermann, Towia ;

Gerhart-Hines, Zachary ;

Puigserver, Pere ;

Haigis, Marcia C. ;

Maratos-Flier, Elefteria ;

Richardson, Andrea L. ;

Schafer, Zachary T. ;

Pandolfi, Pier P. .

JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (09) :3088-3100

[10] The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].

Cerami, Ethan ;

Gao, Jianjiong ;

Dogrusoz, Ugur ;

Gross, Benjamin E. ;

Sumer, Selcuk Onur ;

Aksoy, Buelent Arman ;

Jacobsen, Anders ;

Byrne, Caitlin J. ;

Heuer, Michael L. ;

Larsson, Erik ;

Antipin, Yevgeniy ;

Reva, Boris ;

Goldberg, Arthur P. ;

Sander, Chris ;

Schultz, Nikolaus .

CANCER DISCOVERY, 2012, 2 (05) :401-404

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