PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs

Cell Metabolism

Volumn 26, Issue 5, 2017, Pages 778-787.e5

  Andrzejewski, Sylvia ^a,b   Klimcakova, Eva ^b   Johnson, Radia M ^b   Tabariès, Sébastien ^b   Annis, Matthew G ^b   McGuirk, Shawn ^a,b   Northey, Jason J ^b,c   Chénard, Valérie ^a,b   Sriram, Urshila ^a,b   Papadopoli, David J ^a,b   Siegel, Peter M ^a,b   St Pierre, Julie ^a,b,d  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF OTTAWA   (Canada)

Author keywords

breast cancer; metabolic flexibility; metabolomics; metastasis; metformin; mitochondria; PGC 1 ; phenformin; respirometry; seahorse

Indexed keywords

ANTINEOPLASTIC AGENT; BIGUANIDE; BIGUANIDE DERIVATIVE; METFORMIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PHENFORMIN; ANTIDIABETIC AGENT; PPARGC1A PROTEIN, HUMAN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOENERGY; BONE METASTASIS; CANCER RESISTANCE; CELL INVASION; CELL MIGRATION; COMPARATIVE STUDY; CONCENTRATION RESPONSE; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIVER METASTASIS; LUNG METASTASIS; MDA-MB-231 CELL LINE; METASTATIC BREAST CANCER; MOUSE; NONHUMAN; PHENOTYPIC VARIATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; TUMOR INVASION; ANIMAL; BREAST TUMOR; CELL MOTION; DRUG EFFECT; ENERGY METABOLISM; GENETICS; METABOLISM; METABOLOMICS; METASTASIS; MITOCHONDRION; PATHOLOGY; SCID MOUSE; TUMOR CELL LINE;

ANIMALS; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL MOVEMENT; ENERGY METABOLISM; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; METABOLOMICS; METFORMIN; MICE; MICE, SCID; MITOCHONDRIA; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA COACTIVATOR 1-ALPHA;

EID: 85030629763     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2017.09.006     Document Type: Article

References (46)

1. Andrzejewski, S., Gravel, S.P., Pollak, M., St-Pierre, J., Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab., 2, 2014, 12.
2. Aslakson, C.J., Miller, F.R., Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res. 52 (1992), 1399–1405.
3. Audet-Walsh, É., Papadopoli, D.J., Gravel, S.P., Yee, T., Bridon, G., Caron, M., Bourque, G., Giguère, V., St-Pierre, J., The PGC-1α/ERRα axis represses one-carbon metabolism and promotes sensitivity to anti-folate therapy in breast cancer. Cell Rep. 14 (2016), 920–931.
4. Bhalla, K., Hwang, B.J., Dewi, R.E., Ou, L., Twaddel, W., Fang, H.B., Vafai, S.B., Vazquez, F., Puigserver, P., Boros, L., Girnun, G.D., PGC1α promotes tumor growth by inducing gene expression programs supporting lipogenesis. Cancer Res. 71 (2011), 6888–6898.
5. Bridges, H.R., Sirviö V.A., Agip, A.N., Hirst, J., Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase. BMC Biol., 14, 2016, 65.
6. Carvalho, B.S., Irizarry, R.A., A framework for oligonucleotide microarray preprocessing. Bioinformatics 26 (2010), 2363–2367.
7. Chandel, N.S., Avizonis, D., Reczek, C.R., Weinberg, S.E., Menz, S., Neuhaus, R., Christian, S., Haegebarth, A., Algire, C., Pollak, M., Are metformin doses used in murine cancer models clinically relevant?. Cell Metab. 23 (2016), 569–570.
8. Deblois, G., St-Pierre, J., Giguère, V., The PGC-1/ERR signaling axis in cancer. Oncogene 32 (2013), 3483–3490.
9. 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.
10. Fantin, V.R., St-Pierre, J., Leder, P., Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 9 (2006), 425–434.
11. Giguère, V., Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr. Rev. 29 (2008), 677–696.
12. Gravel, S.P., Andrzejewski, S., Avizonis, D., St-Pierre, J., Stable isotope tracer analysis in isolated mitochondria from mammalian systems. Metabolites 4 (2014), 166–183.
13. Gupta, G.P., Massagué J., Cancer metastasis: building a framework. Cell 127 (2006), 679–695.
14. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
15. Hänzelmann, S., Castelo, R., Guinney, J., GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics, 14, 2013, 7.
16. Hardie, D.G., Molecular pathways: is AMPK a friend or a foe in cancer?. Clin. Cancer Res. 21 (2015), 3836–3840.
17. He, L., Wondisford, F.E., Metformin action: concentrations matter. Cell Metab. 21 (2015), 159–162.
18. Jones, R.G., Thompson, C.B., Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev. 23 (2009), 537–548.
19. Kang, Y., Siegel, P.M., Shu, W., Drobnjak, M., Kakonen, S.M., Cordón-Cardo, C., Guise, T.A., Massagué J., A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3 (2003), 537–549.
20. Keibler, M.A., Wasylenko, T.M., Kelleher, J.K., Iliopoulos, O., Vander Heiden, M.G., Stephanopoulos, G., Metabolic requirements for cancer cell proliferation. Cancer Metab., 4, 2016, 16.
21. Klimcakova, E., Chénard, V., McGuirk, S., Germain, D., Avizonis, D., Muller, W.J., St-Pierre, J., PGC-1α promotes the growth of ErbB2/Neu-induced mammary tumors by regulating nutrient supply. Cancer Res. 72 (2012), 1538–1546.
22. LeBleu, V.S., O'Connell, J.T., Gonzalez Herrera, K.N., Wikman, H., Pantel, K., Haigis, M.C., de Carvalho, F.M., Damascena, A., Domingos Chinen, L.T., Rocha, R.M., et al. PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat. Cell Biol. 16 (2014), 992–1003 1–15.
23. Lehuédé C., Dupuy, F., Rabinovitch, R., Jones, R.G., Siegel, P.M., Metabolic plasticity as a determinant of tumor growth and metastasis. Cancer Res. 76 (2016), 5201–5208.
24. Lou, C., Xiao, M., Cheng, S., Lu, X., Jia, S., Ren, Y., Li, Z., MiR-485-3p and miR-485-5p suppress breast cancer cell metastasis by inhibiting PGC-1α expression. Cell Death Dis., 7, 2016, e2159.
25. Luo, W., Friedman, M.S., Shedden, K., Hankenson, K.D., Woolf, P.J., GAGE: generally applicable gene set enrichment for pathway analysis. BMC Bioinformatics, 10, 2009, 161.
26. Luo, C., Lim, J.H., Lee, Y., Granter, S.R., Thomas, A., Vazquez, F., Widlund, H.R., Puigserver, P., A PGC1α-mediated transcriptional axis suppresses melanoma metastasis. Nature 537 (2016), 422–426.
27. McGuirk, S., Gravel, S.P., Deblois, G., Papadopoli, D.J., Faubert, B., Wegner, A., Hiller, K., Avizonis, D., Akavia, U.D., Jones, R.G., et al. PGC-1α supports glutamine metabolism in breast cancer. Cancer Metab., 1, 2013, 22.
28. Minn, A.J., Gupta, G.P., Siegel, P.M., Bos, P.D., Shu, W., Giri, D.D., Viale, A., Olshen, A.B., Gerald, W.L., Massagué J., Genes that mediate breast cancer metastasis to lung. Nature 436 (2005), 518–524.
29. Mookerjee, S.A., Gerencser, A.A., Nicholls, D.G., Brand, M.D., Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements. J. Biol. Chem. 292 (2017), 7189–7207.
30. Northey, J.J., Chmielecki, J., Ngan, E., Russo, C., Annis, M.G., Muller, W.J., Siegel, P.M., Signaling through ShcA is required for transforming growth factor beta- and Neu/ErbB-2-induced breast cancer cell motility and invasion. Mol. Cell. Biol. 28 (2008), 3162–3176.
31. Northey, J.J., Dong, Z., Ngan, E., Kaplan, A., Hardy, W.R., Pawson, T., Siegel, P.M., Distinct phosphotyrosine-dependent functions of the ShcA adaptor protein are required for transforming growth factor β (TGFβ)-induced breast cancer cell migration, invasion, and metastasis. J. Biol. Chem. 288 (2013), 5210–5222.
32. Pavlova, N.N., Thompson, C.B., The emerging hallmarks of cancer metabolism. Cell Metab. 23 (2016), 27–47.
33. Rose, A.A., Pepin, F., Russo, C., Abou Khalil, J.E., Hallett, M., Siegel, P.M., Osteoactivin promotes breast cancer metastasis to bone. Mol. Cancer Res. 5 (2007), 1001–1014.
34. Rose, A.A., Annis, M.G., Dong, Z., Pepin, F., Hallett, M., Park, M., Siegel, P.M., ADAM10 releases a soluble form of the GPNMB/Osteoactivin extracellular domain with angiogenic properties. PLoS One, 5, 2010, e12093.
35. St-Pierre, J., Buckingham, J.A., Roebuck, S.J., Brand, M.D., Topology of superoxide production from different sites in the mitochondrial electron transport chain. J. Biol. Chem. 277 (2002), 44784–44790.
36. Steeg, P.S., Tumor metastasis: mechanistic insights and clinical challenges. Nat. Med. 12 (2006), 895–904.
37. Steeg, P.S., Targeting metastasis. Nat. Rev. Cancer 16 (2016), 201–218.
38. Tabariès, S., Dong, Z., Annis, M.G., Omeroglu, A., Pepin, F., Ouellet, V., Russo, C., Hassanain, M., Metrakos, P., Diaz, Z., et al. Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes. Oncogene 30 (2011), 1318–1328.
39. Torrano, V., Valcarcel-Jimenez, L., Cortazar, A.R., Liu, X., Urosevic, J., Castillo-Martin, M., Fernández-Ruiz, S., Morciano, G., Caro-Maldonado, A., Guiu, M., et al. The metabolic co-regulator PGC1α suppresses prostate cancer metastasis. Nat. Cell Biol. 18 (2016), 645–656.
40. Ursini-Siegel, J., Rajput, A.B., Lu, H., Sanguin-Gendreau, V., Zuo, D., Papavasiliou, V., Lavoie, C., Turpin, J., Cianflone, K., Huntsman, D.G., Muller, W.J., Elevated expression of DecR1 impairs ErbB2/Neu-induced mammary tumor development. Mol. Cell. Biol. 27 (2007), 6361–6371.
41. Ursini-Siegel, J., Hardy, W.R., Zuo, D., Lam, S.H., Sanguin-Gendreau, V., Cardiff, R.D., Pawson, T., Muller, W.J., ShcA signalling is essential for tumour progression in mouse models of human breast cancer. EMBO J. 27 (2008), 910–920.
42. Vander Heiden, M.G., Targeting cancer metabolism: a therapeutic window opens. Nat. Rev. Drug Discov. 10 (2011), 671–684.
43. Vanharanta, S., Massagué J., Origins of metastatic traits. Cancer Cell 24 (2013), 410–421.
44. Wang, D.S., Jonker, J.W., Kato, Y., Kusuhara, H., Schinkel, A.H., Sugiyama, Y., Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J. Pharmacol. Exp. Ther. 302 (2002), 510–515.
45. Wheaton, W.W., Weinberg, S.E., Hamanaka, R.B., Soberanes, S., Sullivan, L.B., Anso, E., Glasauer, A., Dufour, E., Mutlu, G.M., Budigner, G.S., Chandel, N.S., Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. Elife, 3, 2014, e02242.
46. Zhang, X.H., Wang, Q., Gerald, W., Hudis, C.A., Norton, L., Smid, M., Foekens, J.A., Massagué J., Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16 (2009), 67–78.