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The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion


Autoři: Ting Deng aff001;  Przemyslaw Stempor aff003;  Alex Appert aff003;  Michael Daube aff001;  Julie Ahringer aff003;  Alex Hajnal aff001;  Evelyn Lattmann aff001
Působiště autorů: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse, Zürich, Switzerland aff001;  Molecular Life Science PhD Program, University and ETH Zurich, Zürich aff002;  The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom aff003
Vyšlo v časopise: The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008470
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008470

Souhrn

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest.

Klíčová slova:

Caenorhabditis elegans – Cell cycle and cell division – Gene expression – Gene regulation – Larvae – Notch signaling – RNA interference – Transcription factors


Zdroje

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144: 646–674. doi: 10.1016/j.cell.2011.02.013 21376230

2. Hagedorn EJ, Sherwood DR. Cell invasion through basement membrane: the anchor cell breaches the barrier. Curr Opin Cell Biol. 2011;23: 589–596. doi: 10.1016/j.ceb.2011.05.002 21632231

3. Sherwood DR, Plastino J. Invading, Leading and Navigating Cells in Caenorhabditis elegans: Insights into Cell Movement in Vivo. Genetics. Genetics; 2018;208: 53–78. doi: 10.1534/genetics.117.300082 29301948

4. Seydoux G, Greenwald I. Cell autonomy of lin-12 function in a cell fate decision in C. elegans. Cell. 1989;57: 1237–1245. doi: 10.1016/0092-8674(89)90060-3 2736627

5. Greenwald I, Kovall R. Notch signaling: genetics and structure. WormBook. 2013;: 1–28. doi: 10.1895/wormbook.1.10.2 23355521

6. Attner MA, Keil W, Benavidez JM, Greenwald I. HLH-2/E2A Expression Links Stochastic and Deterministic Elements of a Cell Fate Decision during C. elegans Gonadogenesis. Curr Biol. 2019;29: 3094–3100.e4. doi: 10.1016/j.cub.2019.07.062 31402303

7. Wilkinson HA, Fitzgerald K, Greenwald I. Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision. Cell. 1994;79: 1187–1198. doi: 10.1016/0092-8674(94)90010-8 8001154

8. Matus DQ, Lohmer LL, Kelley LC, Schindler AJ, Kohrman AQ, Barkoulas M, et al. Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression. Elsevier Inc; 2015;35: 162–174. doi: 10.1016/j.devcel.2015.10.002 26506306

9. Anchor Cell Invasion into the Vulval Epithelium in C. elegans.

10. Hwang BJ, Meruelo AD, Sternberg PW. C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion. Development. The Company of Biologists Ltd; 2007;134: 669–679. doi: 10.1242/dev.02769 17215301

11. Rimann I, Hajnal A. Regulation of anchor cell invasion and uterine cell fates by the egl-43 Evi-1 proto-oncogene in Caenorhabditis elegans. Dev Biol. 2007;308: 187–195. doi: 10.1016/j.ydbio.2007.05.023 17573066

12. Maicas M, Vázquez I, Alis R, Marcotegui N, Urquiza L, Cortés-Lavaud X, et al. The MDS and EVI1 complex locus (MECOM) isoforms regulate their own transcription and have different roles in the transformation of hematopoietic stem and progenitor cells. Biochim Biophys Acta Gene Regul Mech. 2017;1860: 721–729. doi: 10.1016/j.bbagrm.2017.03.007 28391050

13. Lu Y, Liang Y, Zheng X, Deng X, Huang W, Zhang G. EVI1 promotes epithelial-to-mesenchymal transition, cancer stem cell features and chemo-/radioresistance in nasopharyngeal carcinoma. J Exp Clin Cancer Res. BioMed Central; 2019;38: 82–17. doi: 10.1186/s13046-019-1077-3 30770775

14. Goyama S, Yamamoto G, Shimabe M, Sato T, Ichikawa M, Ogawa S, et al. Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell Stem Cell. 2008;3: 207–220. doi: 10.1016/j.stem.2008.06.002 18682242

15. Sherwood DR, Butler JA, Kramer JM, Sternberg PW. FOS-1 promotes basement-membrane removal during anchor-cell invasion in C. elegans. Cell. 2005;121: 951–962. doi: 10.1016/j.cell.2005.03.031 15960981

16. Dickinson DJ, Pani AM, Heppert JK, Higgins CD, Goldstein B. Streamlined Genome Engineering with a Self-Excising Drug Selection Cassette. Genetics. 2015;200: 1035–1049. doi: 10.1534/genetics.115.178335 26044593

17. Davis MW, Morton JJ, Carroll D, Jorgensen EM. Gene activation using FLP recombinase in C. elegans. PLoS Genet. 2008;4: e1000028. doi: 10.1371/journal.pgen.1000028 18369447

18. Hwang BJ, Sternberg PW. A cell-specific enhancer that specifies lin-3 expression in the C. elegans anchor cell for vulval development. 2004;131: 143–151.

19. Huang S, Shao G, Liu L. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem. American Society for Biochemistry and Molecular Biology; 1998;273: 15933–15939. doi: 10.1074/jbc.273.26.15933 9632640

20. Zhou B, Wang J, Lee SY, Xiong J, Bhanu N, Guo Q, et al. PRDM16 Suppresses MLL1r Leukemia via Intrinsic Histone Methyltransferase Activity. Mol Cell. 2016;62: 222–236. doi: 10.1016/j.molcel.2016.03.010 27151440

21. Korzelius J, The I, Ruijtenberg S, Portegijs V, Xu H, Horvitz HR, et al. C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability. Dev Biol. 2011;350: 358–369. doi: 10.1016/j.ydbio.2010.12.009 21146520

22. van den Heuvel S. Cell-cycle regulation. WormBook. 2005;: 1–16. doi: 10.1895/wormbook.1.28.1 18050422

23. Park M, Krause MW. Regulation of postembryonic G(1) cell cycle progression in Caenorhabditis elegans by a cyclin D/CDK-like complex. 1999;126: 4849–4860.

24. Spencer SL, Cappell SD, Tsai F-C, Overton KW, Wang CL, Meyer T. The proliferation-quiescence decision is controlled by a bifurcation in CDK2 activity at mitotic exit. Cell. 2013;155: 369–383. doi: 10.1016/j.cell.2013.08.062 24075009

25. van Rijnberk LM, van der Horst SEM, van den Heuvel S, Ruijtenberg S. A dual transcriptional reporter and CDK-activity sensor marks cell cycle entry and progression in C. elegans. Prigent C, editor. PLoS ONE. Public Library of Science; 2017;12: e0171600. doi: 10.1371/journal.pone.0171600 28158315

26. Nusser-Stein S, Beyer A, Rimann I, Adamczyk M, Piterman N, Hajnal A, et al. Cell-cycle regulation of NOTCH signaling during C. elegans vulval development. Mol Syst Biol. 2012;8: 618–614. doi: 10.1038/msb.2012.51 23047528

27. Coraggio F, Püschel R, Marti A, Meister P. Polycomb and Notch signaling regulate cell proliferation potential during Caenorhabditis elegans life cycle. Life Sci Alliance. Life Science Alliance; 2019;2: e201800170. doi: 10.26508/lsa.201800170 30599047

28. Sarov M, Murray JI, Schanze K, Pozniakovski A, Niu W, Angermann K, et al. A genome-scale resource for in vivo tag-based protein function exploration in C. elegans. Cell. 2012;150: 855–866. doi: 10.1016/j.cell.2012.08.001 22901814

29. Hill RJ, Sternberg PW. The gene lin-3 encodes an inductive signal for vulval development in C. elegans. 1992;358: 470–476. doi: 10.1038/358470a0 1641037

30. Chen N, Greenwald I. The lateral signal for LIN-12/Notch in C. elegans vulval development comprises redundant secreted and transmembrane DSL proteins. 2004;6: 183–192.

31. Inoue T, Sherwood DR, Aspöck G, Butler JA, Gupta BP, Kirouac M, et al. Gene expression markers for Caenorhabditis elegans vulval cells. Mech Dev. 2002;119 Suppl 1: S203–9.

32. Hiatt SM, Duren HM, Shyu YJ, Ellis RE, Hisamoto N, Matsumoto K, et al. Caenorhabditis elegans FOS-1 and JUN-1 regulate plc-1 expression in the spermatheca to control ovulation. Tansey WP, editor. Mol Biol Cell. 2009;20: 3888–3895. doi: 10.1091/mbc.E08-08-0833 19570917

33. Wang L, Shen W, Lei S, Matus D, Sherwood D, Wang Z. MIG-10 (Lamellipodin) stabilizes invading cell adhesion to basement membrane and is a negative transcriptional target of EGL-43 in C. elegans. Biochemical and Biophysical Research Communications. 2014;452: 328–333. doi: 10.1016/j.bbrc.2014.08.049 25148942

34. Medwig-Kinney TN, Smith JJ, Palmisano NJ, Tank S, Zhang W, Matus DQ. A developmental gene regulatory network for C. elegans anchor cell invasion. Development. 2020;147: dev185850. doi: 10.1242/dev.185850 31806663

35. Ronchini C, Capobianco AJ. Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol. 2001;21: 5925–5934. doi: 10.1128/MCB.21.17.5925-5934.2001 11486031

36. Cohen B, Shimizu M, Izrailit J, Ng NFL, Buchman Y, Pan JG, et al. Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer. Breast Cancer Res Treat. Springer US; 2010;123: 113–124. doi: 10.1007/s10549-009-0621-9 19915977

37. Baonza A, Freeman M. Control of cell proliferation in the Drosophila eye by Notch signaling. Dev Cell. 2005;8: 529–539. doi: 10.1016/j.devcel.2005.01.019 15809035

38. Brenner S. The Genetics of CAENORHABDITIS ELEGANS. Genetics. 1974;77: 71. 4366476

39. Kamath RS, Ahringer J. Genome-wide RNAi screening in Caenorhabditis elegans. Methods. 2003;30: 313–321. doi: 10.1016/s1046-2023(03)00050-1 12828945

40. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Meth. Nature Publishing Group; 2012;9: 676–682. doi: 10.1038/nmeth.2019 22743772


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