Breast cancers utilize hypoxic glycogen stores via PYGB, the brain isoform of glycogen phosphorylase, to promote metastatic phenotypes
Autoři:
Megan A. Altemus aff001; Laura E. Goo aff002; Andrew C. Little aff002; Joel A. Yates aff002; Hannah G. Cheriyan aff001; Zhi Fen Wu aff002; Sofia D. Merajver aff002
Působiště autorů:
Graduate Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan, United States of America
aff001; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
aff002; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, United States of America
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0220973
Souhrn
In breast cancer, tumor hypoxia has been linked to poor prognosis and increased metastasis. Hypoxia activates transcriptional programs in cancer cells that lead to increased motility and invasion, as well as various metabolic changes. One of these metabolic changes, an increase in glycogen metabolism, has been further associated with protection from reactive oxygen species damage that may lead to premature senescence. Here we report that breast cancer cells significantly increase glycogen stores in response to hypoxia. We found that knockdown of the brain isoform of an enzyme that catalyzes glycogen breakdown, glycogen phosphorylase B (PYGB), but not the liver isoform, PYGL, inhibited glycogen utilization in estrogen receptor negative and positive breast cancer cells; whereas both independently inhibited glycogen utilization in the normal-like breast epithelial cell line MCF-10A. Functionally, PYGB knockdown and the resulting inhibition of glycogen utilization resulted in significantly decreased wound-healing capability in MCF-7 cells and a decrease in invasive potential of MDA-MB-231 cells. Thus, we identify PYGB as a novel metabolic target with potential applications in the management and/or prevention of metastasis in breast cancer.
Klíčová slova:
Biology and life sciences – Cell biology – Genetics – Gene expression – Biochemistry – Research and analysis methods – Enzymology – Enzymes – Proteins – Medicine and health sciences – Oncology – Cancers and neoplasms – Microscopy – Hypoxia – Metastasis – Basic cancer research – Glycobiology – Electron microscopy – Transferases – Enzyme chemistry – Breast tumors – Breast cancer – Transmission electron microscopy – Glycogens – Phosphorylases – Enzyme regulation – Allosteric regulation – Bright field imaging
Zdroje
1. Vaupel P, Mayer A. Hypoxia in cancer: Significance and impact on clinical outcome. Cancer Metastasis Rev 2007. doi: 10.1007/s10555-007-9055-1 17440684
2. Vaupel P, Mayer A, Höckel M. Tumor Hypoxia and Malignant Progression. Methods Enzymol 2004. doi: 10.1016/S0076-6879(04)81023-1
3. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell 2012. doi: 10.1016/j.cell.2012.01.021 22304911
4. Chan DA, Giaccia AJ. Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev 2007. doi: 10.1007/s10555-007-9063-1 17458506
5. Mak P, Leav I, Pursell B, Bae D, Yang X, Taglienti CA, et al. ERβ Impedes Prostate Cancer EMT by Destabilizing HIF-1α and Inhibiting VEGF-Mediated Snail Nuclear Localization: Implications for Gleason Grading. Cancer Cell 2010. doi: 10.1016/j.ccr.2010.02.030 20385358
6. Yang M-H, Wu M-Z, Chiou S-H, Chen P-M, Chang S-Y, Liu C-J, et al. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol 2008. doi: 10.1038/ncb1691 18297062
7. Hiraga T, Kizaka-Kondoh S, Hirota K, Hiraoka M, Yoneda T. Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res 2007. doi: 10.1158/0008-5472.CAN-06-2355 17483326
8. Luo D, Wang J, Li J, Post M. Mouse Snail Is a Target Gene for HIF. Mol Cancer Res 2011. doi: 10.1158/1541-7786.MCR-10-0214 21257819
9. Zhang W, Shi X, Peng Y, Wu M, Zhang P, Xie R, et al. HIF-1α promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer. PLoS One 2015. doi: 10.1371/journal.pone.0129603 26057751
10. Copple BL. Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms. Liver Int 2010. doi: 10.1111/j.1478-3231.2010.02205.x 20158611
11. Chen J, Imanaka N, Chen J, Griffin JD. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer 2010. doi: 10.1038/sj.bjc.6605486 20010940
12. Sahlgren C, Gustafsson M V., Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci 2008. doi: 10.1073/pnas.0802047105 18427106
13. Spivak-Kroizman TR, Hostetter G, Posner R, Aziz M, Hu C, Demeure MJ, et al. Hypoxia triggers hedgehog-mediated tumor-stromal interactions in pancreatic cancer. Cancer Res 2013. doi: 10.1158/0008-5472.CAN-11-1433 23633488
14. Lei J, Ma J, Ma Q, Li X, Liu H, Xu Q, et al. Hedgehog signaling regulates hypoxia induced epithelial to mesenchymal transition and invasion in pancreatic cancer cells via a ligand-independent manner. Mol Cancer 2013. doi: 10.1186/1476-4598-12-66 23786654
15. Zhang H, Wong CCL, Wei H, Gilkes DM, Korangath P, Chaturvedi P, et al. HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 2012. doi: 10.1038/onc.2011.365 21860410
16. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 2010. doi: 10.1038/onc.2009.441 19946328
17. Schindl M, Schoppmann SF, Samonigg H, Hausmaninger H, Kwasny W, Gnant M, et al. Overexpression of hypoxia-inducible factor 1α is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res 2002.
18. Kronblad Å, Jirström K, Rydén L, Nordenskjöld B, Landberg G. Hypoxia inducible factor-1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response. Int J Cancer 2006. doi: 10.1002/ijc.21676 16381002
19. Giatromanolaki A, Koukourakis MI, Simopoulos C, Polychronidis A, Gatter KC, Harris AL, et al. c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1α dependent. Clin Cancer Res 2004. doi: 10.1158/1078-0432.CCR-04-1068 15585632
20. Generali D, Berruti A, Brizzi MP, Campo L, Bonardi S, Wigfield S, et al. Hypoxia-inducible factor-1α expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer. Clin Cancer Res 2006. doi: 10.1158/1078-0432.CCR-05-2690 16899602
21. Bos R, Van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, et al. Levels of hypoxia-inducible factor-1α independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer 2003. doi: 10.1002/cncr.11246 12627523
22. Dales JP, Garcia S, Meunier-Carpentier S, Andrac-Meyer L, Haddad O, Lavaut MN, et al. Overexpression of hypoxia-inducible factor HIF-1α predicts early relapse in breast cancer: Retrospective study in a series of 745 patients. Int J Cancer 2005. doi: 10.1002/ijc.20984 15849727
23. Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature 2012. doi: 10.1038/nature10602 22101433
24. Wise DR, Ward PS, Shay JES, Cross JR, Gruber JJ, Sachdeva UM, et al. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of -ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci 2011. doi: 10.1073/pnas.1117773108 22106302
25. Pavlova NN, Thompson CB. The Emerging Hallmarks of Cancer Metabolism. Cell Metab 2016. doi: 10.1016/j.cmet.2015.12.006 26771115
26. Semenza GL. HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010. doi: 10.1016/j.gde.2009.10.009 19942427
27. Ebert BL, Firth JD, Ratcliffe PJ. Hypoxia and mitochondrial inhibitors regulate expression of glucose transporter-1 via distinct cis-acting sequences. J Biol Chem 1995. doi: 10.1074/jbc.270.49.29083 7493931
28. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 2008. doi: 10.1038/nrc2468 19143055
29. Kim JW, Tchernyshyov I, Semenza GL, Dang C V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006. doi: 10.1016/j.cmet.2006.02.002 16517405
30. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006. doi: 10.1016/j.cmet.2006.01.012 16517406
31. Lu CW, Lin SC, Chen KF, Lai YY, Tsai SJ. Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J Biol Chem 2008. doi: 10.1074/jbc.M803508200 18718909
32. Saez I, Duran J, Sinadinos C, Beltran A, Yanes O, Tevy MF, et al. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia. J Cereb Blood Flow Metab 2014. doi: 10.1038/jcbfm.2014.33 24569689
33. Vigoda A, Mamedova LK, Shneyvays V, Katz A, Shainberg A. Glycogen metabolism in rat heart muscle cultures after hypoxia. Mol Cell Biochem 2003. doi: 10.1023/A:1027302021428
34. Zois CE, Favaro E, Harris AL. Glycogen metabolism in cancer. Biochem Pharmacol 2014. doi: 10.1016/j.bcp.2014.09.001 25219323
35. Pelletier J, Bellot G, Gounon P, Lacas-Gervais S, Pouyssegur J, Mazure NM. Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival. Front Oncol 2012. doi: 10.3389/fonc.2012.00018 22649778
36. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004. doi: 10.1038/nrc1367 15170446
37. Berg, Jeremy M, Tymoczko JL, Gatto GJ, Stryer L. Biochemistry 8th Edition. 2015. doi: 10.1007/978-3-8274-2989-6
38. Beurel E, Grieco SF, Jope RS. Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases. Pharmacol Ther 2015. doi: 10.1016/j.pharmthera.2014.11.016 25435019
39. Rousset M, Fogh J, Zweibaum A. Presence of glycogen and growth–related variations in 58 cultured huma tumor cell lines of various tissue origins. Cancer Res 1981.
40. Favaro E, Bensaad K, Chong MG, Tennant DA, Ferguson DJP, Snell C, et al. Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells. Cell Metab 2012. doi: 10.1016/j.cmet.2012.10.017 23177934
41. Mole DR, Blancher C, Copley RR, Pollard PJ, Gleadle JM, Ragoussis J, et al. Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts. J Biol Chem 2009. doi: 10.1074/jbc.M901790200 19386601
42. Shen GM, Zhang FL, Liu XL, Zhang JW. Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia. FEBS Lett 2010. doi: 10.1016/j.febslet.2010.09.040 20888814
43. Pescador N, Villar D, Cifuentes D, Garcia-Rocha M, Ortiz-Barahona A, Vazquez S, et al. Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1. PLoS One 2010. doi: 10.1371/journal.pone.0009644 20300197
44. Rao GS, Murray S, Ethier SP. Radiosensitization of human breast cancer cells by a novel ErbB family receptor tyrosine kinase inhibitor. Int J Radiat Oncol Biol Phys 2000. doi: 10.1016/S0360-3016(00)01358-4
45. Woods Ignatoski KM, Ethier SP. Constitutive activation of pp125(fak) in newly isolated human breast cancer cell lines. Breast Cancer Res Treat 1999. doi: 10.1023/A:1006135331912
46. Tracey WR, Treadway JLJ, Magee WP, Sutt JC, McPherson RK, Levy CB, et al. Cardioprotective effects of ingliforib, a novel glycogen phosphorylase inhibitor. Am J Physiol Heart Circ Physiol 2004. doi: 10.1152/ajpheart.00652.2003 14615278
Článok vyšiel v časopise
PLOS One
2019 Číslo 9
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
- Ne každé mimoděložní těhotenství musí končit salpingektomií
- Masturbační chování žen v ČR − dotazníková studie
Najčítanejšie v tomto čísle
- Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats
- CH(II), a cerebroprotein hydrolysate, exhibits potential neuro-protective effect on Alzheimer’s disease
- Comparison between Aptima Assays (Hologic) and the Allplex STI Essential Assay (Seegene) for the diagnosis of Sexually transmitted infections
- Assessment of glucose-6-phosphate dehydrogenase activity using CareStart G6PD rapid diagnostic test and associated genetic variants in Plasmodium vivax malaria endemic setting in Mauritania
Zvýšte si kvalifikáciu online z pohodlia domova
Všetky kurzy