Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis

Cell Reports

Volumn 17, Issue 3, 2016, Pages 837-848

  Christen, Stefan ^a,b   Lorendeau, Doriane ^a,b   Schmieder, Roberta ^a,b   Broekaert, Dorien ^a,b   Metzger, Kristine ^a,b   Veys, Koen ^c   Elia, Ilaria ^a,b   Buescher, Joerg Martin ^a,b   Orth, Martin Franz ^d   Davidson, Shawn Michael ^e   Grünewald, Thomas Georg Philipp ^d   De Bock, Katrien ^f   Fendt, Sarah Maria ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b Katholieke Universiteit   (Belgium)

^c UNIVERSITY OF LEUVEN   (Belgium)

^d UNIVERSITY OF MUNICH   (Germany)

^e MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^f ETH ZURICH   (Switzerland)

Author keywords

13C tracer analysis; breast cancer; cancer metabolism; glycolytic metabolism; lung metastasis; microenvironment; mitochondrial pyruvate concentration; pyruvate carboxylase; pyruvate metabolism; TCA cycle anaplerosis

Indexed keywords

ACETYL COENZYME A; ADENOSINE DIPHOSPHATE; ADENOSINE TRIPHOSPHATE; CARBON 13; PYRUVATE CARBOXYLASE; CARBON; PYRUVIC ACID;

ANAPLEROSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; CELL LEVEL; CELL PROLIFERATION; CHEMICAL PHENOMENA; CONTROLLED STUDY; CYTOSOL; ENZYME KINETICS; GENE EXPRESSION; IN VITRO STUDY; LUNG METASTASIS; MATHEMATICAL ANALYSIS; MATHEMATICAL MODEL; MITOCHONDRION; MOUSE; NONHUMAN; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR MICROENVIRONMENT; BREAST TUMOR; CELL COMPARTMENTALIZATION; CITRIC ACID CYCLE; ENZYMOLOGY; FEMALE; HUMAN; ISOTOPE LABELING; LUNG TUMOR; METABOLISM; PATHOLOGY; SECONDARY; TUMOR CELL LINE;

ACETYL COENZYME A; ADENOSINE DIPHOSPHATE; ADENOSINE TRIPHOSPHATE; BREAST NEOPLASMS; CARBON ISOTOPES; CELL COMPARTMENTATION; CELL LINE, TUMOR; CITRIC ACID CYCLE; CYTOSOL; FEMALE; HUMANS; ISOTOPE LABELING; LUNG NEOPLASMS; MITOCHONDRIA; PYRUVATE CARBOXYLASE; PYRUVIC ACID; TUMOR MICROENVIRONMENT;

EID: 84992195909     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.09.042     Document Type: Article

References (38)

1. Adina-Zada, A., Zeczycki, T.N., Attwood, P.V., Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA. Arch. Biochem. Biophys. 519 (2012), 118–130.
2. Antoniewicz, M.R., Kelleher, J.K., Stephanopoulos, G., Elementary metabolite units (EMU): a novel framework for modeling isotopic distributions. Metab. Eng. 9 (2007), 68–86.
3. Boonsaen, T., Rojvirat, P., Surinya, K.H., Wallace, J.C., Jitrapakdee, S., Transcriptional regulation of the distal promoter of the rat pyruvate carboxylase gene by hepatocyte nuclear factor 3β/Foxa2 and upstream stimulatory factors in insulinoma cells. Biochem. J. 405 (2007), 359–367.
4. 13)C metabolite labeling patterns from cells. Curr. Opin. Biotechnol. 34 (2015), 189–201.
5. Chen, J., Lee, H.-J., Wu, X., Huo, L., Kim, S.-J., Xu, L., Wang, Y., He, J., Bollu, L.R., Gao, G., et al. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain. Cancer Res. 75 (2015), 554–565.
6. Cheng, T., Sudderth, J., Yang, C., Mullen, A.R., Jin, E.S., Matés, J.M., DeBerardinis, R.J., Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc. Natl. Acad. Sci. USA 108 (2011), 8674–8679.
7. Compan, V., Pierredon, S., Vanderperre, B., Krznar, P., Marchiq, I., Zamboni, N., Pouyssegur, J., Martinou, J.-C., Monitoring mitochondrial pyruvate carrier activity in real time using a BRET-based biosensor: investigation of the Warburg effect. Mol. Cell 59 (2015), 491–501.
8. Davidson, S.M., Papagiannakopoulos, T., Olenchock, B.A., Heyman, J.E., Keibler, M.A., Luengo, A., Bauer, M.R., Jha, A.K., O'Brien, J.P., Pierce, K.A., et al. Environment impacts the metabolic dependencies of ras-driven non-small cell lung cancer. Cell Metab. 23 (2016), 517–528.
9. Deberardinis, R.J., Sayed, N., Ditsworth, D., Thompson, C.B., Brick by brick: metabolism and tumor cell growth. Curr. Opin. Genet. Dev. 18 (2008), 54–61.
10. Dupuy, F., Tabariès, S., Andrzejewski, S., Dong, Z., Blagih, J., Annis, M.G., Omeroglu, A., Gao, D., Leung, S., Amir, E., et al. PDK1-dependent metabolic reprogramming dictates metastatic potential in breast cancer. Cell Metab. 22 (2015), 577–589.
11. Elia, I., Schmieder, R., Christen, S., Fendt, S.-M., Organ-specific cancer metabolism and its potential for therapy. Handbook Exp. Pharmacol. 233 (2016), 321–353.
12. Fan, T.W.M., Lane, A.N., Higashi, R.M., Farag, M.A., Gao, H., Bousamra, M., Miller, D.M., Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM). Mol. Cancer, 8, 2009, 41.
13. Fendt, S.M., Buescher, J.M., Rudroff, F., Picotti, P., Zamboni, N., Sauer, U., Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity. Mol. Syst. Biol., 6, 2010, 356.
14. Fendt, S.M., Bell, E.L., Keibler, M.A., Davidson, S.M., Wirth, G.J., Fiske, B., Mayers, J.R., Schwab, M., Bellinger, G., Csibi, A., et al. Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism. Cancer Res. 73 (2013), 4429–4438.
15. Fendt, S.M., Bell, E.L., Keibler, M.A., Olenchock, B.A., Mayers, J.R., Wasylenko, T.M., Vokes, N.I., Guarente, L., Vander Heiden, M.G., Stephanopoulos, G., Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells. Nat. Commun., 4, 2013, 2236.
16. Hensley, C.T., Faubert, B., Yuan, Q., Lev-Cohain, N., Jin, E., Kim, J., Jiang, L., Ko, B., Skelton, R., Loudat, L., et al. Metabolic heterogeneity in human lung tumors. Cell 164 (2016), 681–694.
17. Jitrapakdee, S., St. Maurice, M., Rayment, I., Cleland, W.W., Wallace, J.C., Attwood, P.V., Structure, mechanism and regulation of pyruvate carboxylase. Biochem. J. 413 (2008), 369–387.
18. Karlsson, J., Hultén, B., Sjödin, B., Substrate activation and product inhibition of LDH activity in human skeletal muscle. Acta Physiol. Scand. 92 (1974), 21–26.
19. Lorendeau, D., Christen, S., Rinaldi, G., Fendt, S.-M., Metabolic control of signalling pathways and metabolic auto-regulation. Biol. Cell 107 (2015), 251–272.
20. Maher, E.A., Marin-Valencia, I., Bachoo, R.M., Mashimo, T., Raisanen, J., Hatanpaa, K.J., Jindal, A., Jeffrey, F.M., Choi, C., Madden, C., et al. Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed. 25 (2012), 1234–1244.
21. Marchiq, I., Le Floch, R., Roux, D., Simon, M.-P., Pouyssegur, J., Genetic disruption of lactate/H+ symporters (MCTs) and their subunit CD147/BASIGIN sensitizes glycolytic tumor cells to phenformin. Cancer Res. 75 (2015), 171–180.
22. McClure, W.R., Lardy, H.A., Wagner, M., Cleland, W.W., Rat liver pyruvate carboxylase. II. Kinetic studies of the forward reaction. J. Biol. Chem. 246 (1971), 3579–3583.
23. Park, J.O., Rubin, S.A., Xu, Y.-F., Amador-Noguez, D., Fan, J., Shlomi, T., Rabinowitz, J.D., Metabolite concentrations, fluxes and free energies imply efficient enzyme usage. Nat. Chem. Biol. 12 (2016), 482–489.
24. Pavlova, N.N., Thompson, C.B., The emerging hallmarks of cancer metabolism. Cell Metab. 23 (2016), 27–47.
25. Quaegebeur, A., Segura, I., Schmieder, R., Verdegem, D., Decimo, I., Bifari, F., Dresselaers, T., Eelen, G., Ghosh, D., Davidson, S.M., et al. Deletion or inhibition of the oxygen sensor PHD1 protects against ischemic stroke via reprogramming of neuronal metabolism. Cell Metab. 23 (2016), 280–291.
26. San Martín, A., Ceballo, S., Ruminot, I., Lerchundi, R., Frommer, W.B., Barros, L.F., A genetically encoded FRET lactate sensor and its use to detect the Warburg effect in single cancer cells. PLoS ONE, 8, 2013, e57712.
27. Schell, J.C., Olson, K.A., Jiang, L., Hawkins, A.J., Van Vranken, J.G., Xie, J., Egnatchik, R.A., Earl, E.G., DeBerardinis, R.J., Rutter, J., A role for the mitochondrial pyruvate carrier as a repressor of the Warburg effect and colon cancer cell growth. Mol. Cell 56 (2014), 400–413.
28. Scrutton, M.C., White, M.D., Prufication and properties of human liver pyruvate carboxylase. Biochem. Med. 9 (1974), 217–292.
29. Sellers, K., Fox, M.P., Bousamra, M. 2nd, Slone, S.P., Higashi, R.M., Miller, D.M., Wang, Y., Yan, J., Yuneva, M.O., Deshpande, R., et al. Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation. J. Clin. Invest. 125 (2015), 687–698.
30. Strasser, C., Grote, P., Schäuble, K., Ganz, M., Ferrando-May, E., Regulation of nuclear envelope permeability in cell death and survival. Nucleus 3 (2012), 540–551.
31. Taylor, H., Nielsen, J., Keech, D.B., Substrate activation of pyruvate carboxylase by pyruvate. Biochem. Biophys. Res. Commun. 37 (1969), 723–728.
32. Vacanti, N.M., Divakaruni, A.S., Green, C.R., Parker, S.J., Henry, R.R., Ciaraldi, T.P., Murphy, A.N., Metallo, C.M., Regulation of substrate utilization by the mitochondrial pyruvate carrier. Mol. Cell 56 (2014), 425–435.
33. Vanderperre, B., Bender, T., Kunji, E.R.S., Martinou, J.-C., Mitochondrial pyruvate import and its effects on homeostasis. Curr. Opin. Cell Biol. 33 (2015), 35–41.
34. von Glutz, G., Walter, P., Regulation of pyruvate carboxylation by acetyl-CoA in rat liver mitochondria. FEBS Lett. 72 (1976), 299–303.
35. Walter, P., Stucki, J.W., Regulation of pyruvate carboxylase in rat liver mitochondria by adenine nucleotides and short chain fatty acids. Eur J Biochem. 12 (1970), 508–519.
36. Yang, C., Ko, B., Hensley, C.T., Jiang, L., Wasti, A.T., Kim, J., Sudderth, J., Calvaruso, M.A., Lumata, L., Mitsche, M., et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol. Cell 56 (2014), 414–424.
37. Yuneva, M.O., Fan, T.W., Allen, T.D., Higashi, R.M., Ferraris, D.V., Tsukamoto, T., Matés, J.M., Alonso, F.J., Wang, C., Seo, Y., et al. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 15 (2012), 157–170.
38. Zeczycki, T.N., Maurice, M.S., Attwood, P.V., Inhibitors of pyruvate carboxylase. Open Enzyme Inhib. J. 3 (2010), 8–26.