Cancer Cells as Dynamic System – Molecular and Phenotypic Changes During Tumor Formation, Progression and Dissemination
Authors:
L. Sommerová; E. Ondroušková; R. Hrstka
Authors place of work:
Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal:
Klin Onkol 2016; 29(Supplementum 4): 6-11
Category:
Review
doi:
https://doi.org/10.14735/amko20164S6
Summary
Dynamic, punctual and perfectly coordinated cellular response to internal and external stimuli is a crucial prerequisite for adaptation of mammalian cells to all changes that occur during cellular development under physiological conditions. Hijacking this ability is characteristic for tumor cells that are capable to adapt to unfavorable conditions which contribute to the formation and development of cancer during the process of tumor formation and progression. By changing key mechanisms, malignant cells can avoid cell death and thus allow development and spread of the tumor. The changes at the genetic level are manifested by various phenotypic characteristics, through which tumor cells are able to escape defense mechanisms, to acquire resistance to treatment, to invade and to create secondary tumors. In recent years, one of the most studied properties include changes in energy metabolism, when tumor cells specifically control reprogramming of the main metabolic pathways for their own benefit and to satisfy their increased needs not only for energy, but also for building materials required for increased proliferation. To adapt to extracellular conditions, it is necessary that cells undergo morphological changes, where modifications in the cell shape through reorganization of cytoskeletal filaments allow tumor cells to increase their invasiveness and other aggressive features. Clarifying these changes together with understanding of the switch in the genetic program within cancer cells, which allows them to overcome different stages of differentiation from cancer stem cells to fully differentiated cells, would be an important prerequisite for identification of the cancer cell “weaknesses” and may lead to improved cancer treatment. The ability of tumor cells to alter the rules of their own organism thus represents an important challenge for oncological research.
Key words:
cellular reprogramming – cancer cell plasticity – cancer metabolism – tumor heterogeneity – cytoskeleton remodeling – metastasis – oncogenesis
This work was supported by the project MEYS – NPS I – LO1413.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
3. 7. 2016
Accepted:
11. 8. 2016
Zdroje
1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100 (1): 57–70.
2. Klein CA. Selection and adaptation during metastatic cancer progression. Nature 2013; 501 (7467): 365–372. doi: 10.1038/nature12628.
3. Friedl P, Alexander S. Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 2011; 147 (5): 992–1009. doi: 10.1016/j.cell.2011.11.016.
4. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11 (2): 85–95. doi: 10.1038/nrc2981.
5. Warburg O. On the origin of cancer cells. Science 1956; 123 (3191): 309–314.
6. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (5): 646–674. doi: 10.1016/j.cell. 2011.02.013.
7. Granja S, Pinheiro C, Reis RM et al. Glucose addiction in cancer therapy: advances and drawbacks. Curr Drug Metab 2015; 16 (3): 221–242.
8. Kelloff GJ, Hoffman JM, Johnson B et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005; 11 (8): 2785–2808.
9. Schulze A, Harris AL. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature 2012; 491 (7424): 364–373. doi: 10.1038/nature11706.
10. Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 2011; 27: 441–464. doi: 10.1146/annurev-cellbio-092910-154237.
11. Patra KC, Hay N. The pentose phosphate pathway and cancer. Trends Biochem Sci 2014; 39 (8): 347–354. doi: 10.1016/j.tibs.2014.06.005.
12. Possemato R, Marks KM, Shaul YD et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011; 476 (7360): 346–350. doi: 10.1038/nature10350.
13. Mullarky E, Mattaini KR, Vander Heiden MG et al. PHGDH amplification and altered glucose metabolism in human melanoma. Pigment Cell Melanoma Res 2011; 24 (6): 1112–1115. doi: 10.1111/j.1755-148X.2011.00919.x.
14. DeBerardinis RJ, Lum JJ, Hatzivassiliou G et al. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008; 7 (1): 11–20. doi: 10.1016/j.cmet.2007.10.002.
15. DeBerardinis RJ, Mancuso A, Daikhin E et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A 2007; 104 (49): 19345–19350.
16. Dang CV. MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med 2013; 3 (8): pii: a014217. doi: 10.1101/cshperspect.a014217.
17. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324 (5930): 1029–1033. doi: 10.1126/science.1160809.
18. Lane DP. Cancer. p53, guardian of the genome. Nature 1992; 358 (6381): 15–16.
19. Schwartzenberg-Bar-Yoseph F, Armoni M, Karnieli E. The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expression. Cancer Res 2004; 64 (7): 2627–2633.
20. Vousden KH, Ryan KM. p53 and metabolism. Nat Rev Cancer 2009; 9 (10): 691–700. doi: 10.1038/nrc2715.
21. Jiang P, Du W, Wang X et al. p53 regulates biosynthesis through direct inactivation of glucose-6-phosphate dehydrogenase. Nat Cell Biol 2011; 13 (3): 310–316. doi: 10.1038/ncb2172.
22. Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 2008; 8 (9): 705–713. doi: 10.1038/nrc2468.
23. Kim JW, Tchernyshyov I, Semenza GL et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006; 3 (3): 177–185.
24. Kroemer G, Pouyssegur J. Tumor cell metabolism: cancer‘s Achilles‘ heel. Cancer Cell 2008; 13 (6): 472–482. doi: 10.1016/j.ccr.2008.05.005.
25. Schroeder A, Heller DA, Winslow MM et al. Treating metastatic cancer with nanotechnology. Nat Rev Cancer 2012; 12 (1): 39–50. doi: 10.1038/nrc3180.
26. Chan E, Saito A, Honda T et al. The acetylenic tricyclic bis (cyano enone), TBE-31 inhibits non-small cell lung cancer cell migration through direct binding with actin. Cancer Prev Res (Phila) 2014; 7 (7): 727–737. doi: 10.1158/1940-6207.CAPR-13-0403.
27. Müller P, Langenbach A, Kaminski A et al. Modulating the actin cytoskeleton affects mechanically induced signal transduction and differentiation in mesenchymal stem cells. PLoS One 2013; 8 (7): e71283. doi: 10.1371/journal.pone.0071283.
28. Schlessinger K, Hall A, Tolwinski N. Wnt signaling pathways meet Rho GTPases. Genes Dev 2009; 23 (3): 265–277. doi: 10.1101/gad.1760809.
29. Shagieva GS, Domnina LV, Chipysheva TA et al. Actin isoforms and reorganization of adhesion junctions in epithelial-to-mesenchymal transition of cervical carcinoma cells. Biochemistry (Mosc) 2012; 77 (11): 1266–1276. doi: 10.1134/S0006297912110053.
30. Nürnberg A, Kitzing T, Grosse R. Nucleating actin for invasion. Nat Rev Cancer 2011; 11 (3): 177–187. doi: 10.1038/nrc3003.
31. Mattila PK, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat Rev Mol Cell Biol 2008; 9 (6): 446–454. doi: 10.1038/nrm2406.
32. Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta 2007; 1773 (5): 642–652.
33. Leong HS, Robertson AE, Stoletov K et al. Invadopodia are required for cancer cell extravasation and are a therapeutic target for metastasis. Cell Rep 2014; 8 (5): 1558–1570. doi: 10.1016/j.celrep.2014.07.050.
34. Helfand BT, Chang L, Goldman RD. The dynamic and motile properties of intermediate filaments. Annu Rev Cell Dev Biol 2003; 19: 445–467.
35. König K, Meder L, Kröger C et al. Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model. PLoS One 2013; 8 (3): e57996. doi: 10.1371/journal.pone.0057996.
36. Fortier AM, Asselin E, Cadrin M. Keratin 8 and 18 loss in epithelial cancer cells increases collective cell migration and cisplatin sensitivity through claudin1 up-regulation. J Biol Chem 2013; 288 (16): 11555–11571. doi: 10.1074/jbc.M112.428920.
37. Lang SH, Hyde C, Reid IN et al. Enhanced expression of vimentin in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma. Prostate 2002; 52 (4): 253–263.
38. Müsch A. Microtubule organization and function in epithelial cells. Traffic 2004; 5 (1): 1–9.
39. Hernandez P, Tirnauer JS. Tumor suppressor interactions with microtubules: keeping cell polarity and cell division on track. Dis Model Mech 2010; 3 (5–6): 304–315. doi: 10.1242/dmm.004507.
40. Sahai E. Mechanisms of cancer cell invasion. Curr Opin Genet Dev 2005; 15 (1): 87–96.
41. Pierce GB, Wallace C. Differentiation of malignant to benign cells. Cancer Res 1971; 31 (2): 127–134.
42. Lee GY, Shim JS, Cho B et al. Stochastic acquisition of a stem cell-like state and drug tolerance in leukemia cells stressed by radiation. Int J Hematol 2011; 93 (1): 27–35. doi: 10.1007/s12185-010-0734-2.
43. Almendro V, Kim HJ, Cheng YK et al. Genetic and phenotypic diversity in breast tumor metastases. Cancer Res 2014; 74 (5): 1338–1348. doi: 10.1158/0008-5472.CAN-13-2357-T.
44. Almendro V, Cheng YK, Randles A et al. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep 2014; 6 (3): 514–527. doi: 10.1016/j.celrep.2013.12.041.
45. Lipkin G. Plasticity of the cancer cell: implications for epigenetic control of melanoma and other malignancies. J Invest Dermatol 2008; 128 (9): 2152–2155. doi: 10.1038/jid.2008.69.
46. Acloque H, Adams MS, Fishwick K et al. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest 2009; 119 (6): 1438–1449. doi: 10.1172/JCI38019.
47. Thiery JP, Acloque H, Huang RY et al. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139 (5): 871–890. doi: 10.1016/j.cell.2009.11.007.
48. Soda Y, Marumoto T, Friedmann-Morvinski D et al. Transdifferentiation of glioblastoma cells into vascular endothelial cells. Proc Natl Acad Sci U S A 2011; 108 (11): 4274–4280. doi: 10.1073/pnas.1016030108.
49. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126 (4): 663–676.
50. Yamanaka S. Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors. Cell Prolif 2008; 41 (Suppl 1): 51–56. doi: 10.1111/j.1365- 2184.2008.00493.x.
51. Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007; 318 (5858): 1917–1920.
52. Carette JE, Pruszak J, Varadarajan M et al. Generation of iPSCs from cultured human malignant cells. Blood 2010; 115 (20): 4039–4042. doi: 10.1182/blood-2009-07-231 845.
53. Mathieu J, Zhang Z, Zhou W et al. HIF induces human embryonic stem cell markers in cancer cells. Cancer Res 2011; 71 (13): 4640–4652. doi: 10.1158/0008-5472.CAN-10-3320.
54. Miyoshi N, Ishii H, Nagai K et al. Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Natl Acad Sci U S A 2010; 107 (1): 40–45. doi: 10.1073/pnas.0912407107.
Štítky
Paediatric clinical oncology Surgery Clinical oncologyČlánok vyšiel v časopise
Clinical Oncology
2016 Číslo Supplementum 4
- Spasmolytic Effect of Metamizole
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Metamizole in perioperative treatment in children under 14 years – results of a questionnaire survey from practice
- Current Insights into the Antispasmodic and Analgesic Effects of Metamizole on the Gastrointestinal Tract
- Obstacle Called Vasospasm: Which Solution Is Most Effective in Microsurgery and How to Pharmacologically Assist It?
Najčítanejšie v tomto čísle
- The Role of PD-1/PD-L1 Signaling Pathway in Antitumor Immune Response
- Non-Small Cell Lung Cancer – from Immunobiology to Immunotherapy
- Cancer Cells as Dynamic System – Molecular and Phenotypic Changes During Tumor Formation, Progression and Dissemination
- Novel Approaches in DNA Methylation Studies – MS-HRM Analysis and Electrochemistry