Inducible microRNA-200c decreases motility of breast cancer cells and reduces filamin A
Autoři:
Bojan Ljepoja aff001; Christoph Schreiber aff002; Florian A. Gegenfurtner aff003; Jonathan García-Roman aff001; Bianca Köhler aff001; Stefan Zahler aff003; Joachim O. Rädler aff002; Ernst Wagner aff001; Andreas Roidl aff001
Působiště autorů:
Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany
aff001; Faculty of Physics and Center for NanoScience, Ludwig-Maximilians-Universität München, Munich, Germany
aff002; Pharmaceutical Biology, Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich, Germany
aff003
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0224314
Souhrn
Cancer progression and metastases are frequently related to changes of cell motility. Amongst others, the microRNA-200c (miR-200c) was shown to maintain the epithelial state of cells and to hamper migration. Here, we describe two miR-200c inducible breast cancer cell lines, derived from miR-200c knock-out MCF7 cells as well as from the miR-200c-negative MDA-MB-231 cells and report on the emerging phenotypic effects after miR-200s induction. The induction of miR-200c expression seems to effect a rapid reduction of cell motility, as determined by 1D microlane migration assays. Sustained expression of miR200c leads to a changed morphology and reveals a novel mechanism by which miR-200c interferes with cytoskeletal components. We find that filamin A expression is attenuated by miRNA-200c induced downregulation of the transcription factors c-Jun and MRTF/SRF. This potentially novel pathway that is independent of the prominent ZEB axis could lead to a broader understanding of the role that miR200c plays in cancer metastasis.
Klíčová slova:
Transcription factors – Cell motility – MicroRNAs – Metastasis – Breast cancer – Doxycycline – Transcriptional control – Cancer cell migration
Zdroje
1. Riggi N, Aguet M, Stamenkovic I. Cancer Metastasis: A Reappraisal of Its Underlying Mechanisms and Their Relevance to Treatment. Annu Rev Pathol. 2018;13:117–40. Epub 2017/10/27. doi: 10.1146/annurev-pathol-020117-044127 29068753.
2. DeSantis CE, Bray F, Ferlay J, Lortet-Tieulent J, Anderson BO, Jemal A. International Variation in Female Breast Cancer Incidence and Mortality Rates. Cancer Epidemiol Biomarkers Prev. 2015;24(10):1495–506. Epub 2015/09/12. doi: 10.1158/1055-9965.EPI-15-0535 26359465.
3. DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48. Epub 2017/10/04. doi: 10.3322/caac.21412 28972651.
4. Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015;143(4):471–8. Epub 2015/03/18. doi: 10.1309/AJCPYO5FSV3UPEXS 25779997.
5. Mariotto AB, Etzioni R, Hurlbert M, Penberthy L, Mayer M. Estimation of the Number of Women Living with Metastatic Breast Cancer in the United States. Cancer Epidemiol Biomarkers Prev. 2017;26(6):809–15. Epub 2017/05/20. doi: 10.1158/1055-9965.EPI-16-0889 28522448.
6. Campbell K, Casanova J. A common framework for EMT and collective cell migration. Development. 2016;143(23):4291–300. Epub 2016/12/03. doi: 10.1242/dev.139071 27899506.
7. Schaeffer D, Somarelli JA, Hanna G, Palmer GM, Garcia-Blanco MA. Cellular migration and invasion uncoupled: increased migration is not an inexorable consequence of epithelial-to-mesenchymal transition. Mol Cell Biol. 2014;34(18):3486–99. Epub 2014/07/09. doi: 10.1128/MCB.00694-14 25002532.
8. Son H, Moon A. Epithelial-mesenchymal Transition and Cell Invasion. Toxicol Res. 2010;26(4):245–52. Epub 2010/12/01. doi: 10.5487/TR.2010.26.4.245 24278531.
9. Brodersen P, Voinnet O. Revisiting the principles of microRNA target recognition and mode of action. Nature reviews Molecular cell biology. 2009;10(2):141–8. Epub 2009/01/16. doi: 10.1038/nrm2619 19145236.
10. Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nature reviews Molecular cell biology. 2013;14(8):475–88. doi: 10.1038/nrm3611 23800994.
11. Baumjohann D, Ansel KM. MicroRNA-mediated regulation of T helper cell differentiation and plasticity. Nature reviews Immunology. 2013;13(9):666–78. Epub 2013/08/03. doi: 10.1038/nri3494 23907446.
12. Filios SR, Shalev A. beta-Cell MicroRNAs: Small but Powerful. Diabetes. 2015;64(11):3631–44. Epub 2015/10/24. doi: 10.2337/db15-0831
13. Kopp F, Oak PS, Wagner E, Roidl A. miR-200c sensitizes breast cancer cells to doxorubicin treatment by decreasing TrkB and Bmi1 expression. PloS one. 2012;7(11):e50469. doi: 10.1371/journal.pone.0050469 23209748.
14. Ma J, Dong C, Ji C. MicroRNA and drug resistance. Cancer gene therapy. 2010;17(8):523–31. Epub 2010/05/15. doi: 10.1038/cgt.2010.18 20467450.
15. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer. 2010;127(8):1785–94. Epub 2010/01/26. doi: 10.1002/ijc.25191 20099276.
16. Rottiers V, Naar AM. MicroRNAs in metabolism and metabolic disorders. Nature reviews Molecular cell biology. 2012;13(4):239–50. Epub 2012/03/23. doi: 10.1038/nrm3313 22436747.
17. Kopp F, Wagner E, Roidl A. The proto-oncogene KRAS is targeted by miR-200c. Oncotarget. 2014;5(1):185–95. doi: 10.18632/oncotarget.1427 24368337.
18. Humphries B, Yang C. The microRNA-200 family: small molecules with novel roles in cancer development, progression and therapy. Oncotarget. 2015;6(9):6472–98. Epub 2015/03/13. doi: 10.18632/oncotarget.3052 25762624.
19. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature cell biology. 2008;10(5):593–601. Epub 2008/04/01. doi: 10.1038/ncb1722 18376396.
20. Mutlu M, Raza U, Saatci O, Eyupoglu E, Yurdusev E, Sahin O. miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med (Berl). 2016. Epub 2016/04/21. doi: 10.1007/s00109-016-1420-5 27094812.
21. Senfter D, Madlener S, Krupitza G, Mader RM. The microRNA-200 family: still much to discover. Biomol Concepts. 2016;7(5–6):311–9. doi: 10.1515/bmc-2016-0020 27837593.
22. Perdigao-Henriques R, Petrocca F, Altschuler G, Thomas MP, Le MT, Tan SM, et al. miR-200 promotes the mesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes. Oncogene. 2016;35(2):158–72. doi: 10.1038/onc.2015.69 25798844.
23. Jurmeister S, Baumann M, Balwierz A, Keklikoglou I, Ward A, Uhlmann S, et al. MicroRNA-200c represses migration and invasion of breast cancer cells by targeting actin-regulatory proteins FHOD1 and PPM1F. Mol Cell Biol. 2012;32(3):633–51. Epub 2011/12/07. doi: 10.1128/MCB.06212-11 22144583.
24. Howe EN, Cochrane DR, Richer JK. Targets of miR-200c mediate suppression of cell motility and anoikis resistance. Breast Cancer Res. 2011;13(2):R45. doi: 10.1186/bcr2867 21501518.
25. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011;17(9):1101–8. Epub 2011/08/09. doi: 10.1038/nm.2401 21822286.
26. Ljepoja B, Garcia-Roman J, Sommer AK, Frohlich T, Arnold GJ, Wagner E, et al. A proteomic analysis of an in vitro knock-out of miR-200c. Sci Rep. 2018;8(1):6927. Epub 2018/05/04. doi: 10.1038/s41598-018-25240-y 29720730.
27. Nakamura F, Stossel TP, Hartwig JH. The filamins: organizers of cell structure and function. Cell Adh Migr. 2011;5(2):160–9. Epub 2010/12/21. doi: 10.4161/cam.5.2.14401 21169733.
28. Stossel TP, Condeelis J, Cooley L, Hartwig JH, Noegel A, Schleicher M, et al. Filamins as integrators of cell mechanics and signalling. Nature reviews Molecular cell biology. 2001;2(2):138–45. Epub 2001/03/17. doi: 10.1038/35052082 11252955.
29. Baldassarre M, Razinia Z, Burande CF, Lamsoul I, Lutz PG, Calderwood DA. Filamins regulate cell spreading and initiation of cell migration. PloS one. 2009;4(11):e7830. Epub 2009/11/17. doi: 10.1371/journal.pone.0007830 19915675.
30. Schreiber C, Segerer FJ, Wagner E, Roidl A, Radler JO. Ring-Shaped Microlanes and Chemical Barriers as a Platform for Probing Single-Cell Migration. Sci Rep. 2016;6:26858. Epub 2016/06/01. doi: 10.1038/srep26858 27242099.
31. Maiuri P, Terriac E, Paul-Gilloteaux P, Vignaud T, McNally K, Onuffer J, et al. The first World Cell Race. Curr Biol. 2012;22(17):R673–R5. http://dx.doi.org/10.1016/j.cub.2012.07.052.22974990
32. Sinh ND, Endo K, Miyazawa K, Saitoh M. Ets1 and ESE1 reciprocally regulate expression of ZEB1/ZEB2, dependent on ERK1/2 activity, in breast cancer cells. Cancer Sci. 2017;108(5):952–60. Epub 2017/03/02. doi: 10.1111/cas.13214 28247944.
33. Lombaerts M, van Wezel T, Philippo K, Dierssen JW, Zimmerman RM, Oosting J, et al. E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. Br J Cancer. 2006;94(5):661–71. Epub 2006/02/24. doi: 10.1038/sj.bjc.6602996 16495925.
34. Chao YL, Shepard CR, Wells A. Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer. 2010;9:179. Epub 2010/07/09. doi: 10.1186/1476-4598-9-179 20609236.
35. Sun Q, Chen G, Streb JW, Long X, Yang Y, Stoeckert CJ Jr., et al. Defining the mammalian CArGome. Genome Res. 2006;16(2):197–207. Epub 2005/12/21. doi: 10.1101/gr.4108706 16365378.
36. Kumar S, Nag A, Mandal CC. A Comprehensive Review on miR-200c, A Promising Cancer Biomarker with Therapeutic Potential. Current drug targets. 2015;16(12):1381–403. Epub 2015/03/27. doi: 10.2174/1389450116666150325231419 25808651.
37. Chang JT, Wang F, Chapin W, Huang RS. Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas. PloS one. 2016;11(12):e0168284. doi: 10.1371/journal.pone.0168284 27959953.
38. Damiano V, Brisotto G, Borgna S, di Gennaro A, Armellin M, Perin T, et al. Epigenetic silencing of miR-200c in breast cancer is associated with aggressiveness and is modulated by ZEB1. Genes Chromosomes Cancer. 2017;56(2):147–58. doi: 10.1002/gcc.22422 27717206.
39. Kasza KE, Nakamura F, Hu S, Kollmannsberger P, Bonakdar N, Fabry B, et al. Filamin A is essential for active cell stiffening but not passive stiffening under external force. Biophys J. 2009;96(10):4326–35. Epub 2009/05/20. doi: 10.1016/j.bpj.2009.02.035 19450503.
40. Savoy RM, Ghosh PM. The dual role of filamin A in cancer: can’t live with (too much of) it, can’t live without it. Endocr Relat Cancer. 2013;20(6):R341–56. Epub 2013/10/11. doi: 10.1530/ERC-13-0364 24108109.
41. Flanagan LA, Chou J, Falet H, Neujahr R, Hartwig JH, Stossel TP. Filamin A, the Arp2/3 complex, and the morphology and function of cortical actin filaments in human melanoma cells. J Cell Biol. 2001;155(4):511–7. Epub 2001/11/14. doi: 10.1083/jcb.200105148 11706047.
42. Truong T, Shams H, Mofrad MR. Mechanisms of integrin and filamin binding and their interplay with talin during early focal adhesion formation. Integr Biol (Camb). 2015;7(10):1285–96. Epub 2015/07/15. doi: 10.1039/c5ib00133a 26156744.
43. Guo J, Fang W, Sun L, Lu Y, Dou L, Huang X, et al. Reduced miR-200b and miR-200c expression contributes to abnormal hepatic lipid accumulation by stimulating JUN expression and activating the transcription of srebp1. Oncotarget. 2016;7(24):36207–19. Epub 2016/05/12. doi: 10.18632/oncotarget.9183 27166182.
44. Verde P, Casalino L, Talotta F, Yaniv M, Weitzman JB. Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters. Cell Cycle. 2007;6(21):2633–9. Epub 2007/10/25. doi: 10.4161/cc.6.21.4850 17957143.
45. Shaulian E. AP-1—The Jun proteins: Oncogenes or tumor suppressors in disguise? Cell Signal. 2010;22(6):894–9. Epub 2010/01/12. doi: 10.1016/j.cellsig.2009.12.008
46. Xia Y, Karin M. The control of cell motility and epithelial morphogenesis by Jun kinases. Trends Cell Biol. 2004;14(2):94–101. Epub 2004/04/23. doi: 10.1016/j.tcb.2003.12.005 15102441.
47. Norman C, Runswick M, Pollock R, Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell. 1988;55(6):989–1003. Epub 1988/12/23. doi: 10.1016/0092-8674(88)90244-9 3203386.
48. Schwartz B, Marks M, Wittler L, Werber M, Wahrisch S, Nordheim A, et al. SRF is essential for mesodermal cell migration during elongation of the embryonic body axis. Mech Dev. 2014;133:23–35. Epub 2014/07/16. doi: 10.1016/j.mod.2014.07.001 25020278.
49. Hermann MR, Jakobson M, Colo GP, Rognoni E, Jakobson M, Kupatt C, et al. Integrins synergise to induce expression of the MRTF-A-SRF target gene ISG15 for promoting cancer cell invasion. J Cell Sci. 2016;129(7):1391–403. Epub 2016/02/14. doi: 10.1242/jcs.177592 26872785.
50. Kircher P, Hermanns C, Nossek M, Drexler MK, Grosse R, Fischer M, et al. Filamin A interacts with the coactivator MKL1 to promote the activity of the transcription factor SRF and cell migration. Sci Signal. 2015;8(402):ra112. Epub 2015/11/12. doi: 10.1126/scisignal.aad2959 26554816.
51. Peltier HJ, Latham GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA. 2008;14(5):844–52. Epub 2008/04/01. doi: 10.1261/rna.939908 18375788.
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