Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer

Nature Metabolism volume 1, pages 70–85 (2019)Cite this article

Subjects

Abstract

Specific metabolic underpinnings of androgen receptor (AR)-driven growth in prostate adenocarcinoma (PCa) are largely undefined, hindering the development of strategies to leverage the metabolic dependencies of this disease when hormonal manipulations fail. Here we show that the mitochondrial pyruvate carrier (MPC), a critical metabolic conduit linking cytosolic and mitochondrial metabolism, is transcriptionally regulated by AR. Experimental MPC inhibition restricts proliferation and metabolic outputs of the citric acid cycle (TCA) including lipogenesis and oxidative phosphorylation in AR-driven PCa models. Mechanistically, metabolic disruption resulting from MPC inhibition activates the eIF2α/ATF4 integrated stress response (ISR). ISR signalling prevents cell cycle progression while coordinating salvage efforts, chiefly enhancing glutamine assimilation into the TCA, to regain metabolic homeostasis. We confirm that MPC function is operant in PCa tumours in vivo using isotopomeric metabolic flux analysis. In turn, we apply a clinically viable small molecule targeting the MPC, MSDC0160, to pre-clinical PCa models and find that MPC inhibition suppresses tumour growth in hormone-responsive and castrate-resistant conditions. Collectively, our findings characterize the MPC as a tractable therapeutic target in AR-driven prostate tumours.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The MPC is increased in PCa specimens and associated with poor clinical outcomes.
Fig. 2: AR controls the MPC in PCa through transcriptional regulation of MPC2.
Fig. 3: MPC inhibition delays proliferation and disrupts TCA outputs in AR-driven PCa models.
Fig. 4: MPC inhibition disrupts TCA function and prevents cell cycle progression.
Fig. 5: ISR signalling coordinates glutamine uptake and incorporation during MPC suppression.
Fig. 6: MPC inhibition suppresses tumour growth in preclinical models of AR-driven Pca.

Similar content being viewed by others

Data availability

Analyzed RPPA data are available in Supplementary Data 2, analyzed RNA-sequencing data are available in Supplementary Data 3 and raw RNA-sequencing data are available under accession number GSE114708 on the National Center for Biotechnology Information Gene Expression Omnibus database. All other data described, analyzed and represented in the figures present in this study are available from the corresponding authors upon reasonable request.

References

  1. Pavlova, N. N. & Thompson, C. B. The emerging hallmarks of cancer metabolism. Cell. Metab. 23, 27–47 (2016).

    Article  CAS  Google Scholar 

  2. DeBerardinis, R. J. & Chandel, N. S. Fundamentals of cancer metabolism. Sci. Adv. 2, e1600200 (2016).

    Article  Google Scholar 

  3. Keibler, M. A. et al. Metabolic requirements for cancer cell proliferation. Cancer Metab. 4, 16 (2016).

    Article  Google Scholar 

  4. Vander Heiden, M. G. & DeBerardinis, R. J. Understanding the intersections between metabolism and cancer biology. Cell 168, 657–669 (2017).

    Article  Google Scholar 

  5. Wang, Q. et al. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. Cancer Res. 71, 7525–7536 (2011).

    Article  CAS  Google Scholar 

  6. Deblois, G. & Giguère, V. Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond. Nat. Rev. Cancer 13, 27–36 (2013).

    Article  CAS  Google Scholar 

  7. Massie, C. E. et al. The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis. EMBO J. 30, 2719–2733 (2011).

    Article  CAS  Google Scholar 

  8. Mohler, J. L. et al. Prostate cancer, version 1.2016. J. Natl Compr. Canc. Netw. 14, 19–30 (2016).

    Article  Google Scholar 

  9. Mitsiades, N. A road map to comprehensive androgen receptor axis targeting for castration-resistant prostate cancer. Cancer Res. 73, 4599–4605 (2013).

    Article  CAS  Google Scholar 

  10. Scher, H. I. & Sawyers, C. L. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J. Clin. Oncol. 23, 8253–8261 (2005).

    Article  CAS  Google Scholar 

  11. Herzig, S. et al. Identification and functional expression of the mitochondrial pyruvate carrier. Science 337, 93–96 (2012).

    Article  CAS  Google Scholar 

  12. Bricker, D. K. et al. A mitochondrial pyruvate carrier required for pyruvate uptake in yeast, drosophila, and humans. Science 337, 96–100 (2012).

    Article  CAS  Google Scholar 

  13. Schell, J. C. et al. A role for the mitochondrial pyruvate carrier as a repressor of the warburg effect and colon cancer cell growth. Mol. Cell 56, 400–413 (2014).

  14. Costello, L. C. & Franklin, R. B. The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots. Mol. Cancer 5, 17 (2006).

    Article  Google Scholar 

  15. Zadra, G., Photopoulos, C. & Loda, M. The fat side of prostate cancer. Biochim. Biophys. Acta 1831, 1518–1532 (2013).

  16. Cancer Genome Atlas Research Network. The Molecular Taxonomy of Primary Prostate Cancer. Cell 163, 1011–1025 (2015).

  17. Cerami, E. et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2, 401–404 (2012).

    Article  Google Scholar 

  18. Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat. Med. 22, 298–305 (2016).

  19. Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012).

    Article  CAS  Google Scholar 

  20. Chattopadhyay, I. et al. Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures. Oncotarget 8, 10324–10347 (2017).

    Article  Google Scholar 

  21. Hu, R. et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 69, 16–22 (2009).

    Article  CAS  Google Scholar 

  22. Culig, Z. et al. Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system. Br. J. Cancer 81, 242–251 (1999).

    Article  CAS  Google Scholar 

  23. Panigrahi, A. K. et al. SRC-3 coactivator governs dynamic estrogen-induced chromatin looping interactions during transcription. Mol. Cell 70, 679–694.e7 (2018).

    Article  CAS  Google Scholar 

  24. Pomerantz, M. M. et al. The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis. Nat. Genet. 47, 1346–1351 (2015).

    Article  CAS  Google Scholar 

  25. Stelloo, S. et al. Androgen receptor profiling predicts prostate cancer outcome. EMBO Mol. Med. 7, 1450–1464 (2015).

    Article  CAS  Google Scholar 

  26. Sullivan, L. B., Gui, D. Y. & Vander Heiden, M. G. Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. Nat. Rev. Cancer 16, 680–693 (2016).

    Article  CAS  Google Scholar 

  27. Halestrap, A. P. The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors. Biochem. J. 148, 85–96 (1975).

    Article  CAS  Google Scholar 

  28. Anantharaman, A. & Friedlander, T. W. Targeting the androgen receptor in metastatic castrate-resistant prostate cancer: a review. Urol. Oncol. Semin. Orig. Investig. 34, 356–367 (2016).

    Article  CAS  Google Scholar 

  29. Hildyard, J. C. W., Ammälä, C., Dukes, I. D., Thomson, S. A. & Halestrap, A. P. Identification and characterisation of a new class of highly specific and potent inhibitors of the mitochondrial pyruvate carrier. Biochim. Biophys. Acta 1707, 221–230 (2005).

    Article  CAS  Google Scholar 

  30. Halestrap, A. P. The monocarboxylate transporter family—structure and functional characterization. IUBMB Life 64, 1–9 (2012).

    Article  CAS  Google Scholar 

  31. Polański, R. et al. Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer. Clin. Cancer Res. 20, 926–937 (2014).

    Article  Google Scholar 

  32. Davidson, S. M. et al. Environment impacts the metabolic dependencies of ras-driven non-small cell lung cancer. Cell. Metab. 23, 517–528 (2016).

    Article  CAS  Google Scholar 

  33. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).

    Article  CAS  Google Scholar 

  34. Pakos-Zebrucka, K. et al. The integrated stress response. EMBO Rep. 17, 1374–1395 (2016).

    Article  CAS  Google Scholar 

  35. Hamanaka, R. B., Bennett, B. S., Cullinan, S. B. & Diehl, J. A. PERK and GCN2 contribute to eIF2α phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway. Mol. Biol. Cell 16, 5493–5501 (2005).

    Article  CAS  Google Scholar 

  36. Yang, C. et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol. Cell 56, 414–424 (2014).

    Article  CAS  Google Scholar 

  37. Faubert, B. et al. Lactate metabolism in human lung tumors. Cell 171, 358–371.e9 (2017).

    Article  CAS  Google Scholar 

  38. Hui, S. et al. Glucose feeds the TCA cycle via circulating lactate. Nature 551, 115–118 (2017).

  39. Herbst, E. A. F., George, M. A. J., Brebner, K., Holloway, G. P. & Kane, D. A. Lactate is oxidized outside of the mitochondrial matrix in rodent brain. Appl. Physiol. Nutr. Metab. 43, 467–474 (2017).

  40. Chen, Y. J. et al. Lactate metabolism is associated with mammalian mitochondria. Nat. Chem. Biol. 12, 937–943 (2016).

    Article  CAS  Google Scholar 

  41. Corbet, C. et al. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels direct antitumor and radiosensitizing effects. Nat. Commun. 9, 1208 (2018).

    Article  Google Scholar 

  42. Liu, I. J., Zafar, M. B., Lai, Y.-H., Segall, G. M. & Terris, M. K. Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer. Urology 57, 108–111 (2001).

  43. Nelson, S. J. et al. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C]pyruvate. Sci. Transl. Med. 5, 198ra108 (2013).

    Article  Google Scholar 

  44. Shah, R. et al. An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer’s disease. Curr. Alzheimer Res. 11, 564–573 (2014).

    Article  CAS  Google Scholar 

  45. Colca, J. R. et al. Clinical proof-of-concept study with MSDC-0160, a prototype mTOT-modulating insulin sensitizer. Clin. Pharmacol. Ther. 93, 352–359 (2013).

    Article  CAS  Google Scholar 

  46. Ghosh, A. et al. Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinsons disease. Sci. Transl. Med. 8, 368ra174 (2016).

    Article  Google Scholar 

  47. Kolenko, V., Teper, E., Kutikov, A. & Uzzo, R. Zinc and zinc transporters in prostate carcinogenesis. Nat. Rev. Urol. 10, 219–226 (2013).

    Article  CAS  Google Scholar 

  48. Schell, J. C. et al. Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism. Nat. Cell Biol. 19, 1027–1036 (2017).

    Article  CAS  Google Scholar 

  49. Schulte, M. L. et al. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat. Med. 24, 194–202 (2018).

    Article  CAS  Google Scholar 

  50. McCommis, K. S. et al. Targeting the mitochondrial pyruvate carrier attenuates fibrosis in a mouse model of nonalcoholic steatohepatitis. Hepatology 65, 1543–1556 (2017).

    Article  CAS  Google Scholar 

  51. Divakaruni, A. S. et al. Inhibition of the mitochondrial pyruvate carrier protects from excitotoxic neuronal death. J. Cell. Biol. 216, 1091–1105 (2017).

    Article  CAS  Google Scholar 

  52. Rauckhorst, A. J. et al. The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity. Mol. Metab. 6, 1468–1479 (2017).

    Article  CAS  Google Scholar 

  53. Nancolas, B. et al. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem. J. 473, 929–936 (2016).

    Article  CAS  Google Scholar 

  54. Divakaruni, A. S. et al. Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. Proc. Natl. Acad. Sci. USA 110, 5422–5427 (2013).

  55. Lyles, B. E., Akinyeke, T. O., Moss, P. E. & Stewart, L. V. Thiazolidinediones regulate expression of cell cycle proteins in human prostate cancer cells via PPARγ-dependent and PPARγ-independent pathways. Cell Cycle 8, 268–277 (2009).

  56. Fröhlich, E. & Wahl, R. Chemotherapy and chemoprevention by thiazolidinediones. Biomed Res. Int. 2015, 845340 (2015).

  57. Suzuki, S. et al. Pioglitazone, a peroxisome proliferator-activated receptor γ agonist, suppresses rat prostate carcinogenesis. Int. J. Mol. Sci. 17, 2071 (2016).

  58. Hensley, C. T. T. et al. Metabolic heterogeneity in human lung tumors. Cell 164, 681–694 (2016).

    Article  CAS  Google Scholar 

  59. Taylor, B. S. et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 18, 11–22 (2010).

    Article  CAS  Google Scholar 

  60. Morris, J. K. A formaldehyde glutaraldehyde fixative of high osmolality for use in electron microscopy. J. Cell. Biol. 27, 1A–149A (1965).

    Article  Google Scholar 

  61. Darzynkiewicz, Z. & Juan, G. DNA content measurement for DNA ploidy and cell cycle analysis. Curr. Protoc. Cytom. 00, 7.5.1–7.5.24 (2001).

    Article  Google Scholar 

  62. Bae, S., Park, J. & Kim, J. S. Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics 30, 1473–1475 (2014).

    Article  CAS  Google Scholar 

  63. Putluri, N. et al. Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells. PLoS ONE 6, e21417 (2011).

    Article  CAS  Google Scholar 

  64. Kettner, N. M. et al. Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis article circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis. Cancer Cell 30, 909–924 (2016).

  65. Ramirez, M. S. et al. Radial spectroscopic MRI of hyperpolarized [1-13C] pyruvate at 7 tesla. Magn. Reson. Med. 72, 986–995 (2014).

    Article  CAS  Google Scholar 

  66. Bankson, J. A. et al. Kinetic modeling and constrained reconstruction of hyperpolarized [1-13C]-pyruvate offers improved metabolic imaging of tumors. Cancer Res. 75, 4708–4717 (2015).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the US National Institutes of Health (NIH): grant no. R21CA205257 (S.E.M.), F30CA196108 (D.A.B.), K01DK096093, R03DK105006, R01DK114356 (S.M.H.), R01CA211150 (J.A.B.), R01CA220297 (N.P.), F30AG050412 (H.M.-S.), U01CA167234 (A.S.), PO1DK113954 and HD08818 (B.W.O.), the Prostate Cancer Foundation (S.E.M.), The Caroline Weiss Law Scholar Foundation (S.E.M.), The MD Anderson Physician Scientist Development Program (S.E.M.), and the Cancer Research and Prevention Institute of Texas (RP140021-P5 (J.A.B.) and RP140106 (MDACC)). D.A.B. is a C. Thomas Caskey Scholar. D.A.B., H.M.-S. and M.P.H. are supported by the Baylor College of Medicine (BCM) Medical Scientist Training Program. S.M.H. is supported by the BCM Bridge to Independence Program and the Alkek Center for Molecular Discovery. M.P.H. is supported by the B.R.A.S.S. program, and the Robert and Janice McNair Foundation. V.P., N.P., A.S., K.R. and C.C. are supported by the CPRIT Core Facility Support Award RP120092, the NCI Cancer Center Support Grant P30CA125123, intramural funds from the Dan L. Duncan Cancer Center, and Alkek Center for Molecular Discovery. Additional support is from the American Cancer Society (127430-RSG-15-105-01-CNE to N.P.), CPRIT (RP150451 to A.S.) and GE Healthcare (J.A.B and C.W). The BCM Metabolomics Core is a designated Agilent Technologies Center for Excellence in Mass Spectrometry. We thank the following BCM Cores: Human Tissue Acquisition and Pathology (NCI-CA125123), Mouse Metabolism (director P. Saha), Integrated Microscopy (NCI-CA125123, NIDDK-56338-13/15, CPRIT RP150578, and the John S. Dunn Gulf Coast Consortium for Chemical Genomics), Cytometry and Cell Sorting (director J. Sederstrom, NIAID P30AI036211, NCI P30CA125123, and NCRR S10RR024574). We thank the M.D.A.C.C. Characterized Cell Line Core and Small Animal Imaging Facility (P30-CA016672). We thank J. Colca and the Metabolic Solutions Development Company for generously providing MSDC0160. We thank D. Townley for TEM imaging and B. Krishnan, M. Finegold, and G. Stoica for reviewing TEM images. We thank J. Rutter, D. Moore and A. Means for insightful conversations related to this manuscript. We acknowledge the joint participation by the Diana Helis Henry Medical Research Foundation through its direct engagement in the continuous active conduct of medical research (S.E.M. and A.S.).

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    David A. Bader, Sean M. Hartig, Vasanta Putluri, Christopher Foley, Mark P. Hamilton, Eric A. Smith, Pradip K. Saha, Anil Panigrahi, Lin Zong, Kimal Rajapakshe, Cristian Coarfa, Arun Sreekumar, Nicholas Mitsiades, Michael M. Ittmann, Bert W. O’Malley, Nagireddy Putluri & Sean E. McGuire

  2. Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, TX, USA

    Sean M. Hartig & Pradip K. Saha

  3. Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Vasanta Putluri, Kimal Rajapakshe, Cristian Coarfa, Arun Sreekumar & Nagireddy Putluri

  4. Department of Imaging Physics, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Christopher Walker & James A. Bankson

  5. Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA

    Heidi Martini-Stoica

  6. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Rui Chen

  7. Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX, USA

    Nicholas Mitsiades

  8. Department of Pathology, Baylor College of Medicine, Houston, TX, USA

    Michael M. Ittmann

  9. Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sean E. McGuire

Authors
  1. David A. Bader
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sean M. Hartig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vasanta Putluri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher Foley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mark P. Hamilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eric A. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pradip K. Saha
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anil Panigrahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christopher Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lin Zong
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Heidi Martini-Stoica
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kimal Rajapakshe
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Cristian Coarfa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Arun Sreekumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Nicholas Mitsiades
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. James A. Bankson
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Michael M. Ittmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Bert W. O’Malley
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Nagireddy Putluri
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Sean E. McGuire
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.A.B. and S.E.M. conceptualized the study. D.A.B., S.M.H. and S.E.M. designed experiments. D.A.B. wrote the manuscript with editorial input from all authors. D.A.B. performed all experiments with assistance as noted: S.M.H. assisted with immunofluorescence. A.S., V.P. and N.P. assisted with mass spectroscopy measurements. L.Z., C.F., E.A.S. and H.M.-S. assisted with animal tumour growth experiments. P.K.S. performed U13C glucose infusions. B.W.O. and A.P. provided reagents and performed in vitro transcription experiments. J.A.B. and C.W. performed hyperpolarized pyruvate imaging. M.P.H., C.C. and K.R. assisted with clinical dataset analysis. R.C. performed RNA sequencing. K.R. and C.C. assisted with RPPA data analysis, RNA sequencing data analysis, and AR ChIP sequencing integrative analysis. M.M.I. provided clinical specimens. N.M. provided prostate cancer models. All work was performed under the supervision of S.E.M.

Corresponding authors

Correspondence to David A. Bader or Sean E. McGuire.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7

Reporting Summary

Supplementary Data 1

Informatic nomination and candidate genes

Supplementary Data 2

Reverse phase protein array (RPPA) data from ABL cells treated with UK5099

Supplementary Data 3

Analyzed RNA-sequencing data from ABL cells treated with UK5099

Supplementary Data 4

Reagent-related materials including antibodies, primers, sgRNA sequences, STR authentication data, and mycoplasma screening data

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bader, D.A., Hartig, S.M., Putluri, V. et al. Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer. Nat Metab 1, 70–85 (2019). https://doi.org/10.1038/s42255-018-0002-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42255-018-0002-y

Keywords

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer