#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Cytoneme-mediated signaling essential for tumorigenesis


Autoři: Sol Fereres aff001;  Ryo Hatori aff001;  Makiko Hatori aff001;  Thomas B. Kornberg aff001
Působiště autorů: Cardiovascular Research Institute, University of California, San Francisco, California, United States of America aff001
Vyšlo v časopise: Cytoneme-mediated signaling essential for tumorigenesis. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008415
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008415

Souhrn

Communication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor models and tested several genetic loss-of-function conditions that impair cytoneme-mediated signaling. Neuroglian, capricious, Irk2, SCAR, and diaphanous are genes that cytonemes require during normal development. Neuroglian and Capricious are cell adhesion proteins, Irk2 is a potassium channel, and SCAR and Diaphanous are actin-binding proteins, and the only process to which they are known to contribute jointly is cytoneme-mediated signaling. We observed that diminished function of any one of these genes suppressed tumor growth and increased organism survival. We also noted that EGFR-expressing tumor discs have abnormally extensive tracheation (respiratory tubes) and ectopically express Branchless (Bnl, a FGF) and FGFR. Bnl is a known inducer of tracheation that signals by a cytoneme-mediated process in other contexts, and we determined that exogenous over-expression of dominant negative FGFR suppressed and tumor growth. Our results are consistent with the idea that cytonemes move signaling proteins between tumor and stromal cells and that cytoneme-mediated signaling is required for tumor growth and malignancy.

Klíčová slova:

Carcinogenesis – Drosophila melanogaster – Epithelial cells – Larvae – Myoblasts – DPP signaling cascade – Paracrine signaling – Stromal cells


Zdroje

1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100: 57–70. doi: 10.1016/s0092-8674(00)81683-9 10647931

2. Roswall P, Bocci M, Bartoschek M, Li H, Kristiansen G, Jansson S, et al. Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nature Medicine. 2018;24: 463–473. doi: 10.1038/nm.4494 29529015

3. Pietras K, Östman A. Hallmarks of cancer: Interactions with the tumor stroma. Experimental Cell Research. 2010. pp. 1324–1331. doi: 10.1016/j.yexcr.2010.02.045 20211171

4. Sonoshita M, Cagan RL. Modeling Human Cancers in Drosophila. Current topics in developmental biology. 2017. pp. 287–309. doi: 10.1016/bs.ctdb.2016.07.008 28057303

5. Huang H, Liu S, Kornberg TB. Glutamate signaling at cytoneme synapses. Science. 2019;363: 948–955. doi: 10.1126/science.aat5053 30819957

6. Kornberg TB, Roy S. Communicating by touch—neurons are not alone. Trends Cell Biol. 2014;24: 370–376. doi: 10.1016/j.tcb.2014.01.003 24560610

7. Roy S, Huang H, Liu S, Kornberg TB. Cytoneme-Mediated Contact-Dependent Transport of the Drosophila Decapentaplegic Signaling Protein. Science. 2014;343: 1244624–1244624. doi: 10.1126/science.1244624 24385607

8. González-Méndez L, Seijo-Barandiarán I, Guerrero I. Cytoneme-mediated cell-cell contacts for hedgehog reception. eLife. 2017;6. doi: 10.7554/eLife.24045 28825565

9. Huang H, Kornberg TB. Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium. eLife. 2015;4: e06114. doi: 10.7554/eLife.06114 25951303

10. Sibilia M, Kroismayr R, Lichtenberger BM, Natarajan A, Hecking M, Holcmann M. The epidermal growth factor receptor: From development to tumorigenesis. Differentiation. 2007. pp. 770–787. doi: 10.1111/j.1432-0436.2007.00238.x 17999740

11. Jiang X, Couchman JR. Perlecan and Tumor Angiogenesis. Journal of Histochemistry and Cytochemistry. 2003. pp. 1393–1410. doi: 10.1177/002215540305101101 14566013

12. Herranz H, Weng R, Cohen SM. Crosstalk between epithelial and mesenchymal tissues in tumorigenesis and imaginal disc development. Current Biology. 2014;24: 1476–1484. doi: 10.1016/j.cub.2014.05.043 24980505

13. Read RD, Goodfellow PJ, Mardis ER, Novak N, Armstrong JR, Cagan RL. A drosophila model of multiple endocrine neoplasia type 2. Genetics. 2005;171: 1057–1081. doi: 10.1534/genetics.104.038018 15965261

14. Dar AC, Das TK, Shokat KM, Cagan RL. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature. 2012;486: 80–84. doi: 10.1038/nature11127 22678283

15. Kornberg TB. Cytonemes and the dispersion of morphogens. Wiley Interdisciplinary Reviews: Developmental Biology. 2014. pp. 445–463. doi: 10.1002/wdev.151 25186102

16. Shiga Y, Tanaka-Matakatsu M, Hayashi S. A nuclear GFP/beta-galactosidase fusion protein as a marker for morphogenesis in living Drosophila. Development Growth & Differentiation. 1996;38: 99–106. doi: 10.1046/j.1440-169X.1996.00012.x

17. Entchev E V, Schwabedissen A, González-Gaitán M. Gradient formation of the TGF-beta homolog Dpp. Cell. 2000;103: 981–91. doi: 10.1016/s0092-8674(00)00200-2 11136982

18. Bischoff M, Gradilla AC, Seijo I, Andres G, Rodriguez-Navas C, Gonzalez-Mendez L, et al. Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia. Nat Cell Biol. 2013;15: 1269–1281. doi: 10.1038/ncb2856 24121526

19. Huang H, Kornberg TB. Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes. eLife. 2016;5. doi: 10.7554/eLife.18979 27591355

20. Chen W, Huang H, Hatori R, Kornberg TB. Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc. Development. 2017; doi: 10.1242/dev.149856 28743798

21. Du L, Sohr A, Yan G, Roy S. Feedback regulation of cytoneme-mediated transport shapes a tissue-specific FGF morphogen gradient. eLife. 2018;7. doi: 10.7554/eLife.38137 30328809

22. González-Méndez L, Seijo-Barandiarán I, Guerrero I. Cytoneme-mediated cell-cell contacts for Hedgehog reception. Elife. 2017;6. doi: 10.7554/eLife.24045 28825565

23. Blochlinger K, Jan LY, Jan YN. Postembryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila. Development (Cambridge, England). 1993;117: 441–50. doi: 10.1101/gad.5.7.1124

24. Sharma P, McNeill H. Fat and Dachsous Cadherins. Progress in Molecular Biology and Translational Science. 2013;116: 215–235. doi: 10.1016/B978-0-12-394311-8.00010-8 23481197

25. Guha A, Lin L, Kornberg TB. Regulation of Drosophila matrix metalloprotease Mmp2 is essential for wing imaginal disc:trachea association and air sac tubulogenesis. Developmental Biology. 2009;335: 317–326. doi: 10.1016/j.ydbio.2009.09.005 19751719

26. Sato M, Kornberg TB. FGF is an essential mitogen and chemoattractant for the air sacs of the Drosophila tracheal system. Developmental Cell. 2002;3: 195–207. doi: 10.1016/S1534-5807(02)00202-2 12194851

27. Du L, Zhou A, Patel A, Rao M, Anderson K, Roy S. Unique patterns of organization and migration of FGF-expressing cells during Drosophila morphogenesis. Developmental Biology. 2017;427: 35–48. doi: 10.1016/j.ydbio.2017.05.009 28502613

28. Grifoni D, Sollazzo M, Fontana E, Froldi F, Pession A. Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark. Sci Rep. 2015;5: 9061. doi: 10.1038/srep09061 25762498

29. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473: 298–307. doi: 10.1038/nature10144 21593862

30. Quail D, Joyce J. Microenvironmental regulation of tumor progression and metastasis. Nature medicine. 2013;19: 1423–1437. doi: 10.1038/nm.3394 24202395

31. Presta M, Chiodelli P, Giacomini A, Rusnati M, Ronca R. Fibroblast growth factors (FGFs) in cancer: FGF traps as a new therapeutic approach. Pharmacology and Therapeutics. 2017. pp. 171–187. doi: 10.1016/j.pharmthera.2017.05.013 28564583

32. Heinemann V, Reni M, Ychou M, Richel DJ, Macarulla T, Ducreux M. Tumour-stroma interactions in pancreatic ductal adenocarcinoma: Rationale and current evidence for new therapeutic strategies. Cancer Treatment Reviews. 2014. pp. 118–128. doi: 10.1016/j.ctrv.2013.04.004 23849556

33. Lou E, Zhai E, Sarkari A, Desir S, Wong P, Iizuka Y, et al. Cellular and Molecular Networking Within the Ecosystem of Cancer Cell Communication via Tunneling Nanotubes. Frontiers in cell and developmental biology. 2018;6: 95. doi: 10.3389/fcell.2018.00095 30333973

34. Connor Y, Tekleab S, Nandakumar S, Walls C, Tekleab Y, Husain A, et al. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype. Nature Communications. 2015; doi: 10.1038/ncomms9671 26669454

35. Yamashita YM, Inaba M, Buszczak M. Specialized Intercellular Communications via Cytonemes and Nanotubes. Annu Rev Cell Dev Biol. 2018;34: 59–84. doi: 10.1146/annurev-cellbio-100617-062932 30074816

36. González-Méndez L, Gradilla A-C, Guerrero I. The cytoneme connection: direct long-distance signal transfer during development. Development. 2019;146. doi: 10.1242/dev.174607 31068374

37. Kornberg TB. A Path to Pattern. Curr Top Dev Biol. 2016;116: 551–567. doi: 10.1016/bs.ctdb.2015.11.026 26970641

38. Eom DS, Bain EJ, Patterson LB, Grout ME, Parichy DM. Long-distance communication by specialized cellular projections during pigment pattern development and evolution. eLife. 2015;4. doi: 10.7554/eLife.12401 26701906

39. Sanders TA, Llagostera E, Barna M. Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning. Nature. 2013;497: 628–632. doi: 10.1038/nature12157 23624372

40. Stanganello E, Hagemann AIH, Mattes B, Sinner C, Meyen D, Weber S, et al. Filopodia-based Wnt transport during vertebrate tissue patterning. Nature communications. 2015;6: 5846. doi: 10.1038/ncomms6846 25556612

41. Inaba M, Buszczak M, Yamashita YM. Nanotubes mediate niche-stem-cell signalling in the Drosophila testis. Nature. 2015;523: 329–332. doi: 10.1038/nature14602 26131929

42. Bangi E, Murgia C, Teague AGS, Sansom OJ, Cagan RL. Functional exploration of colorectal cancer genomes using Drosophila. Nature Communications. 2016;7. doi: 10.1038/ncomms13615 27897178

43. Levine BD, Cagan RL. Drosophila Lung Cancer Models Identify Trametinib plus Statin as Candidate Therapeutic. Cell Reports. 2016; doi: 10.1016/j.celrep.2015.12.105 26832408

44. Markstein M, Dettorre S, Cho J, Neumuller RA, Craig-Muller S, Perrimon N. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proceedings of the National Academy of Sciences. 2014;111: 4530–4535. doi: 10.1073/pnas.1401160111 24616500

45. Taniguchi H, Shishido E, Takeichi M, Nose A. Functional dissection of Drosophila Capricious: Its novel roles in neuronal pathfinding and selective synapse formation. Journal of Neurobiology. 2000;42: 104–116. doi: 10.1002/(SICI)1097-4695(200001)42:1<104::AID-NEU10>3.0.CO;2-V 10623905

46. Reichman-Fried M, Shilo BZ. Breathless, a Drosophila FGF receptor homolog, is required for the onset of tracheal cell migration and tracheole formation. Mechanisms of Development. 1995; doi: 10.1016/0925-4773(95)00407-R

47. Dahal GR, Pradhan SJ, Bates EA. Inwardly rectifying potassium channels influence Drosophila wing morphogenesis by regulating Dpp release. Development. 2017;144: 2771–2783. doi: 10.1242/dev.146647 28684627

48. Ramirez-Weber FA, Casso DJ, Aza-Blanc P, Tabata T, Kornberg TB. Hedgehog signal transduction in the posterior compartment of the Drosophila wing imaginal disc. Molecular Cell. 2000;6: 479–485. doi: 10.1016/s1097-2765(00)00046-0 10983993

49. Teleman AA, Cohen SM. Dpp gradient formation in the Drosophila wing imaginal disc. Cell. 2000;103: 971–980. doi: 10.1016/s0092-8674(00)00199-9 11136981

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2019 Číslo 9
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#