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DOI: 10.1055/a-0805-9113
Mechanisms of Metastasis and Cell Mobility – The Role of Metabolism
Artikel in mehreren Sprachen: English | deutschPublikationsverlauf
received 05. November 2018
revised 22. November 2018
accepted 23. November 2018
Publikationsdatum:
18. Februar 2019 (online)
![](https://www.thieme-connect.de/media/gebfra/201902/lookinside/thumbnails/10-1055-a-0805-9113_gf_en-1.jpg)
Abstract
Tumour metastasis is responsible for more than 90% of tumour-associated mortality. About one third of breast cancer patients in the early stage develop metastases. The transformation in tumour development referred to as the “metastatic cascade” or “metastatic cycle” is a complex and multi-stage event. While it is generally recognised that epithelial-mesenchymal transformation (EMT) plays a crucial role in cancer progression and metastasis, the metabolic events in this process have received little attention to date. We would therefore like to provide a brief overview here of the influence of the metabolism on the progression and metastasis of tumours.
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References/Literatur
- 1 Berg JM, Stryer L, Tymoczko JL. et al. Biochemistry. New York: WH Freeman; 2015
- 2 Nordstrom L, Achanna S, Naka K. et al. Fetal and maternal lactate increase during active second stage of labour. BJOG 2001; 108: 263-268
- 3 Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 2012; 21: 297-308
- 4 Warburg O. Über den Stoffwechsel der Carcinomzelle. Naturwissenschaften 1924; 12: 1131-1137
- 5 Warburg O, Wind F, Negelein E. THE METABOLISM OF TUMORS IN THE BODY. J Gen Physiol 1927; 8: 519-530
- 6 Marin-Hernandez A, Gallardo-Perez JC, Hernandez-Resendiz I. et al. Hypoglycemia Enhances Epithelial-Mesenchymal Transition and Invasiveness, and Restrains the Warburg Phenotype, in Hypoxic HeLa Cell Cultures and Microspheroids. J Cell Physiol 2017; 232: 1346-1359
- 7 Warburg O. On the origin of cancer cells. Science 1956; 123: 309-314
- 8 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674
- 9 Koivunen P, Lee S, Duncan CG. et al. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 2012; 483: 484-488
- 10 Xu W, Yang H, Liu Y. et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 2011; 19: 17-30
- 11 Guo J, Wang B, Fu Z. et al. Hypoxic Microenvironment Induces EMT and Upgrades Stem-Like Properties of Gastric Cancer Cells. Technol Cancer Res Treat 2016; 15: 60-68
- 12 Matsuoka J, Yashiro M, Doi Y. et al. Hypoxia stimulates the EMT of gastric cancer cells through autocrine TGFbeta signaling. PLoS One 2013; 8: e62310
- 13 Shen X, Xue Y, Si Y. et al. The unfolded protein response potentiates epithelial-to-mesenchymal transition (EMT) of gastric cancer cells under severe hypoxic conditions. Med Oncol 2015; 32: 447
- 14 Zhang H, Sun L, Xiao X. et al. Kruppel-like factor 8 contributes to hypoxia-induced MDR in gastric cancer cells. Cancer Sci 2014; 105: 1109-1115
- 15 Zhou J, Li K, Gu Y. et al. Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. Biochem Biophys Res Commun 2011; 415: 348-354
- 16 Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11: 85-95
- 17 Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science 2001; 292: 504-507
- 18 Dai C, Sun F, Zhu C. et al. Tumor environmental factors glucose deprivation and lactic acidosis induce mitotic chromosomal instability–an implication in aneuploid human tumors. PLoS One 2013; 8: e63054
- 19 Wu H, Ding Z, Hu D. et al. Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death. J Pathol 2012; 227: 189-199
- 20 Xie J, Wu H, Dai C. et al. Beyond Warburg effect–dual metabolic nature of cancer cells. Sci Rep 2014; 4: 4927
- 21 Eckert MA, Santiago-Medina M, Lwin TM. et al. ADAM12 induction by Twist1 promotes tumor invasion and metastasis via regulation of invadopodia and focal adhesions. J Cell Sci 2017; 130: 2036-2048
- 22 Shi L, Pan H, Liu Z. et al. Roles of PFKFB3 in cancer. Signal Transduct Target Ther 2017; 2: 17044
- 23 Draoui N, de Zeeuw P, Carmeliet P. Angiogenesis revisited from a metabolic perspective: role and therapeutic implications of endothelial cell metabolism. Open Biol 2017; 7: pii:170219
- 24 Hu X, Chao M, Wu H. Central role of lactate and proton in cancer cell resistance to glucose deprivation and its clinical translation. Signal Transduct Target Ther 2017; 2: 16047
- 25 Liang J, Shao SH, Xu ZX. et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 2007; 9: 218-224
- 26 Schild T, Low V, Blenis J. et al. Unique Metabolic Adaptations Dictate Distal Organ-Specific Metastatic Colonization. Cancer Cell 2018; 33: 347-354
- 27 Lopez-Soto A, Gonzalez S, Smyth MJ. et al. Control of Metastasis by NK Cells. Cancer Cell 2017; 32: 135-154
- 28 Nieto MA, Huang RY, Jackson RA. et al. EMT: 2016. Cell 2016; 166: 21-45
- 29 Brabletz T, Kalluri R, Nieto MA. et al. EMT in cancer. Nat Rev Cancer 2018; 18: 128-134
- 30 Pastushenko I, Brisebarre A, Sifrim A. et al. Identification of the tumour transition states occurring during EMT. Nature 2018; 556: 463-468
- 31 Thompson EW, Nagaraj SH. Transition states that allow cancer to spread. Nature 2018; 556: 442-444
- 32 Polasik A, Tzschaschel M, Schochter F. et al. Circulating Tumour Cells, Circulating Tumour DNA and Circulating MicroRNA in Metastatic Breast Carcinoma – What is the Role of Liquid Biopsy in Breast Cancer?. Geburtsh Frauenheilk 2017; 77: 1291-1298
- 33 Massague J, Obenauf AC. Metastatic colonization by circulating tumour cells. Nature 2016; 529: 298-306
- 34 Obenauf AC, Massague J. Surviving at a Distance: Organ-Specific Metastasis. Trends Cancer 2015; 1: 76-91
- 35 Mathew A, Rajagopal PS, Villgran V. et al. Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast. Geburtsh Frauenheilk 2017; 77: 660-666
- 36 Lehuede C, Dupuy F, Rabinovitch R. et al. Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis. Cancer Res 2016; 76: 5201-5208
- 37 Zhu A, Lee D, Shim H. Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol 2011; 38: 55-69
- 38 Zhu A, Shim H. Current molecular imaging positron emitting radiotracers in oncology. Nucl Med Mol Imaging 2011; 45: 1-14
- 39 Mazurek S, Boschek CB, Hugo F. et al. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 2005; 15: 300-308
- 40 Dong G, Mao Q, Xia W. et al. PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncol Lett 2016; 11: 1980-1986
- 41 He X, Du S, Lei T. et al. PKM2 in carcinogenesis and oncotherapy. Oncotarget 2017; 8: 110656-110670
- 42 Vander Heiden MG. Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 2011; 10: 671-684
- 43 Luengo A, Gui DY, Vander Heiden MG. Targeting Metabolism for Cancer Therapy. Cell Chem Biol 2017; 24: 1161-1180
- 44 Taran FA, Schneeweiss A, Lux MP. et al. Update Breast Cancer 2018 (Part 1) – Primary Breast Cancer and Biomarkers. Geburtsh Frauenheilk 2018; 78: 237-245
- 45 Schneeweiss A, Lux MP, Janni W. et al. Update Breast Cancer 2018 (Part 2) – Advanced Breast Cancer, Quality of Life and Prevention. Geburtsh Frauenheilk 2018; 78: 246-259