Girdin is a component of the lateral polarity protein network restricting cell dissemination


Autoři: Cornélia Biehler aff001;  Li-Ting Wang aff003;  Myriam Sévigny aff001;  Alexandra Jetté aff001;  Clémence L. Gamblin aff001;  Rachel Catterall aff003;  Elise Houssin aff001;  Luke McCaffrey aff003;  Patrick Laprise aff001
Působiště autorů: Centre de Recherche sur le Cancer, Université Laval, Québec, Canada aff001;  Centre de Recherche sur le Cancer, Universitaire de Québec-UL, Québec, Canada aff001;  axe oncologie du Centre de Recherche du Centre Hospitalier, Universitaire de Québec-UL, Québec, Canada aff002;  Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada aff003;  Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada aff004
Vyšlo v časopise: Girdin is a component of the lateral polarity protein network restricting cell dissemination. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008674
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008674

Souhrn

Epithelial cell polarity defects support cancer progression. It is thus crucial to decipher the functional interactions within the polarity protein network. Here we show that Drosophila Girdin and its human ortholog (GIRDIN) sustain the function of crucial lateral polarity proteins by inhibiting the apical kinase aPKC. Loss of GIRDIN expression is also associated with overgrowth of disorganized cell cysts. Moreover, we observed cell dissemination from GIRDIN knockdown cysts and tumorspheres, thereby showing that GIRDIN supports the cohesion of multicellular epithelial structures. Consistent with these observations, alteration of GIRDIN expression is associated with poor overall survival in subtypes of breast and lung cancers. Overall, we discovered a core mechanism contributing to epithelial cell polarization from flies to humans. Our data also indicate that GIRDIN has the potential to impair the progression of epithelial cancers by preserving cell polarity and restricting cell dissemination.

Klíčová slova:

Caco-2 cells – Cell polarity – Confocal microscopy – Cytoskeletal proteins – Drosophila melanogaster – Embryos – Epithelial cells – Morphogenesis


Zdroje

1. Harris TJ, Tepass U. Adherens junctions: from molecules to morphogenesis. Nature reviews Molecular cell biology. 2010;11(7):502–14. Epub 2010/06/24. nrm2927 [pii] doi: 10.1038/nrm2927 20571587.

2. Desai R, Sarpal R, Ishiyama N, Pellikka M, Ikura M, Tepass U. Monomeric alpha-catenin links cadherin to the actin cytoskeleton. Nature cell biology. 2013;15(3):261–73. Epub 2013/02/19. doi: 10.1038/ncb2685 23417122.

3. Houssin E, Tepass U, Laprise P. Girdin-mediated interactions between cadherin and the actin cytoskeleton are required for epithelial morphogenesis in Drosophila. Development. 2015;142(10):1777–84. doi: 10.1242/dev.122002 25968313.

4. Wang X, Enomoto A, Weng L, Mizutani Y, Abudureyimu S, Esaki N, et al. Girdin/GIV regulates collective cancer cell migration by controlling cell adhesion and cytoskeletal organization. Cancer Sci. 2018. doi: 10.1111/cas.13795 30194792.

5. Wang Y, Kaneko N, Asai N, Enomoto A, Isotani-Sakakibara M, Kato T, et al. Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2011;31(22):8109–22. Epub 2011/06/03. 31/22/8109 [pii] doi: 10.1523/JNEUROSCI.1130-11.2011 21632933.

6. McGill MA, McKinley RF, Harris TJ. Independent cadherin-catenin and Bazooka clusters interact to assemble adherens junctions. The Journal of cell biology. 2009;185(5):787–96. Epub 2009/05/27. jcb.200812146 [pii] doi: 10.1083/jcb.200812146 19468069; PubMed Central PMCID: PMC2711589.

7. Muller HA, Wieschaus E. armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila. The Journal of cell biology. 1996;134(1):149–63. doi: 10.1083/jcb.134.1.149 8698811; PubMed Central PMCID: PMC2120925.

8. Bilder D, Schober M, Perrimon N. Integrated activity of PDZ protein complexes regulates epithelial polarity. Nature cell biology. 2003;5(1):53–8. Epub 2003/01/03. doi: 10.1038/ncb897 [pii]. 12510194.

9. Harris TJ, Peifer M. Adherens junction-dependent and -independent steps in the establishment of epithelial cell polarity in Drosophila. The Journal of cell biology. 2004;167(1):135–47. Epub 2004/10/14. jcb.200406024 [pii] doi: 10.1083/jcb.200406024 15479740; PubMed Central PMCID: PMC2172516.

10. Tepass U. The Apical Polarity Protein Network in Drosophila Epithelial Cells: Regulation of Polarity, Junctions, Morphogenesis, Cell Growth, and Survival. Annu Rev Cell Dev Biol. 2012. Epub 2012/08/14. doi: 10.1146/annurev-cellbio-092910-154033 22881460.

11. Wodarz A, Ramrath A, Grimm A, Knust E. Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. The Journal of cell biology. 2000;150(6):1361–74. doi: 10.1083/jcb.150.6.1361 10995441; PubMed Central PMCID: PMC2150710.

12. Harris TJ, Peifer M. The positioning and segregation of apical cues during epithelial polarity establishment in Drosophila. The Journal of cell biology. 2005;170(5):813–23. Epub 2005/09/01. jcb.200505127 [pii] doi: 10.1083/jcb.200505127 16129788; PubMed Central PMCID: PMC2171335.

13. Aguilar-Aragon M, Elbediwy A, Foglizzo V, Fletcher GC, Li VSW, Thompson BJ. Pak1 Kinase Maintains Apical Membrane Identity in Epithelia. Cell Rep. 2018;22(7):1639–46. doi: 10.1016/j.celrep.2018.01.060 29444419; PubMed Central PMCID: PMC5847184.

14. Fletcher GC, Lucas EP, Brain R, Tournier A, Thompson BJ. Positive feedback and mutual antagonism combine to polarize Crumbs in the Drosophila follicle cell epithelium. Current biology: CB. 2012;22(12):1116–22. Epub 2012/06/05. doi: 10.1016/j.cub.2012.04.020 [pii]. 22658591.

15. Hutterer A, Betschinger J, Petronczki M, Knoblich JA. Sequential roles of Cdc42, Par-6, aPKC, and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Developmental cell. 2004;6(6):845–54. Epub 2004/06/05. doi: 10.1016/j.devcel.2004.05.003 [pii]. 15177032.

16. Peterson FC, Penkert RR, Volkman BF, Prehoda KE. Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition. Mol Cell. 2004;13(5):665–76. doi: 10.1016/s1097-2765(04)00086-3 15023337.

17. Krahn MP, Buckers J, Kastrup L, Wodarz A. Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia. The Journal of cell biology. 2010;190(5):751–60. Epub 2010/09/08. jcb.201006029 [pii] doi: 10.1083/jcb.201006029 20819933; PubMed Central PMCID: PMC2935580.

18. Morais-de-Sa E, Mirouse V, St Johnston D. aPKC phosphorylation of Bazooka defines the apical/lateral border in Drosophila epithelial cells. Cell. 2010;141(3):509–23. Epub 2010/05/04. S0092-8674(10)00193-5 [pii] doi: 10.1016/j.cell.2010.02.040 20434988; PubMed Central PMCID: PMC2885938.

19. Walther RF, Pichaud F. Crumbs/DaPKC-dependent apical exclusion of Bazooka promotes photoreceptor polarity remodeling. Current biology: CB. 2010;20(12):1065–74. Epub 2010/05/25. S0960-9822(10)00561-0 [pii] doi: 10.1016/j.cub.2010.04.049 20493700.

20. David DJ, Wang Q, Feng JJ, Harris TJ. Bazooka inhibits aPKC to limit antagonism of actomyosin networks during amnioserosa apical constriction. Development. 2013;140(23):4719–29. doi: 10.1242/dev.098491 24173807.

21. Soriano EV, Ivanova ME, Fletcher G, Riou P, Knowles PP, Barnouin K, et al. aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization. Developmental cell. 2016;38(4):384–98. doi: 10.1016/j.devcel.2016.07.018 27554858; PubMed Central PMCID: PMC4998004.

22. McCaffrey LM, Montalbano J, Mihai C, Macara IG. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. Cancer Cell. 2012;22(5):601–14. doi: 10.1016/j.ccr.2012.10.003 23153534; PubMed Central PMCID: PMC3500525.

23. Hong Y. aPKC: the Kinase that Phosphorylates Cell Polarity. F1000Res. 2018;7. doi: 10.12688/f1000research.13350.2 29983916; PubMed Central PMCID: PMC6020718.

24. Gamblin CL, Hardy EJ, Chartier FJ, Bisson N, Laprise P. A bidirectional antagonism between aPKC and Yurt regulates epithelial cell polarity. The Journal of cell biology. 2014;204(4):487–95. Epub 2014/02/12. doi: 10.1083/jcb.201308032 24515345; PubMed Central PMCID: PMC3926957.

25. Gamblin CL, Parent-Prevost F, Jacquet K, Biehler C, Jette A, Laprise P. Oligomerization of the FERM-FA protein Yurt controls epithelial cell polarity. The Journal of cell biology. 2018. doi: 10.1083/jcb.201803099 30082297.

26. Laprise P, Tepass U. Novel insights into epithelial polarity proteins in Drosophila. Trends Cell Biol. 2011. Epub 2011/05/03. S0962-8924(11)00039-0 [pii] doi: 10.1016/j.tcb.2011.03.005. 21530265.

27. Laprise P, Beronja S, Silva-Gagliardi NF, Pellikka M, Jensen AM, McGlade CJ, et al. The FERM protein Yurt is a negative regulatory component of the Crumbs complex that controls epithelial polarity and apical membrane size. Developmental cell. 2006;11(3):363–74. Epub 2006/09/05. S1534-5807(06)00257-7 [pii] doi: 10.1016/j.devcel.2006.06.001 16950127.

28. Laprise P, Lau KM, Harris KP, Silva-Gagliardi NF, Paul SM, Beronja S, et al. Yurt, Coracle, Neurexin IV and the Na(+),K(+)-ATPase form a novel group of epithelial polarity proteins. Nature. 2009;459(7250):1141–5. Epub 2009/06/26. nature08067 [pii] doi: 10.1038/nature08067 19553998.

29. Drummond ML, Prehoda KE. Molecular Control of Atypical Protein Kinase C: Tipping the Balance between Self-Renewal and Differentiation. J Mol Biol. 2016;428(7):1455–64. doi: 10.1016/j.jmb.2016.03.003 26992354; PubMed Central PMCID: PMC4848065.

30. Tanentzapf G, Tepass U. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nature cell biology. 2003;5(1):46–52. Epub 2003/01/03. doi: 10.1038/ncb896 [pii]. 12510193.

31. Yamanaka T, Horikoshi Y, Izumi N, Suzuki A, Mizuno K, Ohno S. Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. Journal of cell science. 2006;119(Pt 10):2107–18. Epub 2006/04/28. jcs.02938 [pii] doi: 10.1242/jcs.02938 16638806.

32. Sotillos S, Diaz-Meco MT, Caminero E, Moscat J, Campuzano S. DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila. The Journal of cell biology. 2004;166(4):549–57. Epub 2004/08/11. doi: 10.1083/jcb.200311031 [pii]. 15302858; PubMed Central PMCID: PMC2172211.

33. David DJ, Tishkina A, Harris TJ. The PAR complex regulates pulsed actomyosin contractions during amnioserosa apical constriction in Drosophila. Development. 2010;137(10):1645–55. Epub 2010/04/16. doi: 10.1242/dev.044107 20392741.

34. Archibald A, Al-Masri M, Liew-Spilger A, McCaffrey L. Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling. Molecular biology of the cell. 2015;26(20):3578–95. doi: 10.1091/mbc.E15-05-0265 26269582; PubMed Central PMCID: PMC4603929.

35. Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nature cell biology. 2000;2(8):540–7. doi: 10.1038/35019582 10934475.

36. Ohara K, Enomoto A, Kato T, Hashimoto T, Isotani-Sakakibara M, Asai N, et al. Involvement of Girdin in the determination of cell polarity during cell migration. PloS one. 2012;7(5):e36681. Epub 2012/05/11. doi: 10.1371/journal.pone.0036681 [pii]. 22574214; PubMed Central PMCID: PMC3344933.

37. Goldstein B, Macara IG. The PAR proteins: fundamental players in animal cell polarization. Developmental cell. 2007;13(5):609–22. Epub 2007/11/06. S1534-5807(07)00385-1 [pii] doi: 10.1016/j.devcel.2007.10.007 17981131.

38. Sasaki K, Kakuwa T, Akimoto K, Koga H, Ohno S. Regulation of epithelial cell polarity by PAR-3 depends on Girdin transcription and Girdin-Galphai3 signaling. Journal of cell science. 2015;128(13):2244–58. doi: 10.1242/jcs.160879 25977476.

39. Aznar N, Patel A, Rohena CC, Dunkel Y, Joosen LP, Taupin V, et al. AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin. Elife. 2016;5. doi: 10.7554/eLife.20795 27813479; PubMed Central PMCID: PMC5119889.

40. Sigurbjornsdottir S, Mathew R, Leptin M. Molecular mechanisms of de novo lumen formation. Nature reviews Molecular cell biology. 2014;15(10):665–76. doi: 10.1038/nrm3871 25186133.

41. Jaffe AB, Kaji N, Durgan J, Hall A. Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis. The Journal of cell biology. 2008;183(4):625–33. doi: 10.1083/jcb.200807121 19001128; PubMed Central PMCID: PMC2582895.

42. Hao Y, Du Q, Chen X, Zheng Z, Balsbaugh JL, Maitra S, et al. Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Current biology: CB. 2010;20(20):1809–18. Epub 2010/10/12. doi: 10.1016/j.cub.2010.09.032 20933426; PubMed Central PMCID: PMC2963683.

43. Thaiparambil JT, Eggers CM, Marcus AI. AMPK regulates mitotic spindle orientation through phosphorylation of myosin regulatory light chain. Molecular and cellular biology. 2012;32(16):3203–17. doi: 10.1128/MCB.00418-12 22688514; PubMed Central PMCID: PMC3434549.

44. Lu MS, Johnston CA. Molecular pathways regulating mitotic spindle orientation in animal cells. Development. 2013;140(9):1843–56. doi: 10.1242/dev.087627 23571210; PubMed Central PMCID: PMC3631962.

45. Durgan J, Kaji N, Jin D, Hall A. Par6B and atypical PKC regulate mitotic spindle orientation during epithelial morphogenesis. The Journal of biological chemistry. 2011;286(14):12461–74. doi: 10.1074/jbc.M110.174235 21300793; PubMed Central PMCID: PMC3069449.

46. Bilder D. Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors. Genes & development. 2004;18(16):1909–25. Epub 2004/08/18. doi: 10.1101/gad.121160418/16/1909 [pii]. 15314019.

47. Tepass U, Gruszynski-DeFeo E, Haag TA, Omatyar L, Torok T, Hartenstein V. shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia. Genes & development. 1996;10(6):672–85. Epub 1996/03/15. doi: 10.1101/gad.10.6.672 8598295.

48. Oda H, Uemura T, Shiomi K, Nagafuchi A, Tsukita S, Takeichi M. Identification of a Drosophila homologue of alpha-catenin and its association with the armadillo protein. The Journal of cell biology. 1993;121(5):1133–40. doi: 10.1083/jcb.121.5.1133 8501118; PubMed Central PMCID: PMC2119693.

49. Peifer M. The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction. Journal of cell science. 1993;105 (Pt 4):993–1000. 8227220.

50. Betschinger J, Mechtler K, Knoblich JA. The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature. 2003;422(6929):326–30. Epub 2003/03/12. doi: 10.1038/nature01486 [pii]. 12629552.

51. Bailey MJ, Prehoda KE. Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs. Developmental cell. 2015;35(2):199–210. doi: 10.1016/j.devcel.2015.09.016 26481050; PubMed Central PMCID: PMC4624610.

52. Hardiman KM. Update on Sporadic Colorectal Cancer Genetics. Clin Colon Rectal Surg. 2018;31(3):147–52. doi: 10.1055/s-0037-1602234 29720900; PubMed Central PMCID: PMC5929885.

53. Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, et al. Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. The Journal of cell biology. 2001;152(6):1183–96. doi: 10.1083/jcb.152.6.1183 11257119; PubMed Central PMCID: PMC2199212.

54. Nagai-Tamai Y, Mizuno K, Hirose T, Suzuki A, Ohno S. Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells. Genes Cells. 2002;7(11):1161–71. doi: 10.1046/j.1365-2443.2002.00590.x 12390250.

55. Suzuki A, Ohno S. The PAR-aPKC system: lessons in polarity. Journal of cell science. 2006;119(Pt 6):979–87. Epub 2006/03/10. 119/6/979 [piidoi: 10.1242/jcs.02898 16525119.

56. Ghosh P, Rangamani P, Kufareva I. The GAPs, GEFs, GDIs and …now, GEMs: New kids on the heterotrimeric G protein signaling block. Cell cycle. 2017;16(7):607–12. doi: 10.1080/15384101.2017.1282584 28287365; PubMed Central PMCID: PMC5397260.

57. Aznar N, Kalogriopoulos N, Midde KK, Ghosh P. Heterotrimeric G protein signaling via GIV/Girdin: Breaking the rules of engagement, space, and time. Bioessays. 2016;38(4):379–93. doi: 10.1002/bies.201500133 26879989; PubMed Central PMCID: PMC5123561.

58. Ghosh P. The stress polarity pathway: AMPK 'GIV'-es protection against metabolic insults. Aging (Albany NY). 2017;9(2):303–14. doi: 10.18632/aging.101179 28209925; PubMed Central PMCID: PMC5361665.

59. Garcia-Marcos M, Ghosh P, Farquhar MG. GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates Akt signaling. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(9):3178–83. Epub 2009/02/13. doi: 10.1073/pnas.0900294106 19211784; PubMed Central PMCID: PMC2651282.

60. Weng L, Enomoto A, Ishida-Takagishi M, Asai N, Takahashi M. Girding for migratory cues: roles of the Akt substrate Girdin in cancer progression and angiogenesis. Cancer Sci. 2010;101(4):836–42. Epub 2010/02/06. CAS1487 [pii] doi: 10.1111/j.1349-7006.2009.01487.x 20132219.

61. Garcia-Marcos M, Ghosh P, Farquhar MG. GIV/Girdin transmits signals from multiple receptors by triggering trimeric G protein activation. The Journal of biological chemistry. 2015;290(11):6697–704. doi: 10.1074/jbc.R114.613414 25605737; PubMed Central PMCID: PMC4358093.

62. Parker PJ, Justilien V, Riou P, Linch M, Fields AP. Atypical protein kinase Ciota as a human oncogene and therapeutic target. Biochem Pharmacol. 2014;88(1):1–11. doi: 10.1016/j.bcp.2013.10.023 24231509; PubMed Central PMCID: PMC3944347.

63. Lin WH, Asmann YW, Anastasiadis PZ. Expression of polarity genes in human cancer. Cancer Inform. 2015;14(Suppl 3):15–28. doi: 10.4137/CIN.S18964 25991909; PubMed Central PMCID: PMC4390136.

64. Jeanes A, Gottardi CJ, Yap AS. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene. 2008;27(55):6920–9. doi: 10.1038/onc.2008.343 19029934; PubMed Central PMCID: PMC2745643.

65. Halaoui R, McCaffrey L. Rewiring cell polarity signaling in cancer. Oncogene. 2015;34(8):939–50. doi: 10.1038/onc.2014.59 24632617.

66. Gateff E, Schneiderman HA. Developmental capacities of benign and malignant neoplasms ofDrosophila. Wilhelm Roux Arch Entwickl Mech Org. 1974;176(1):23–65. doi: 10.1007/BF00577830 28304815.

67. Chou TB, Perrimon N. The autosomal FLP-DFS technique for generating germline mosaics in Drosophila melanogaster. Genetics. 1996;144(4):1673–9. Epub 1996/12/01. 8978054; PubMed Central PMCID: PMC1207718.

68. Sollier K, Gaude HM, Chartier FJ, Laprise P. Rac1 controls epithelial tube length through the apical secretion and polarity pathways. Biol Open. 2015;5(1):49–54. doi: 10.1242/bio.015727 26700724; PubMed Central PMCID: PMC4728308.

69. Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 2010;123(3):725–31. doi: 10.1007/s10549-009-0674-9 20020197.

Štítky
Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics


2020 Číslo 3

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Kurz originály vs. generika
nový kurz
Autoři:

Klinická farmakokinetika betablokátorů
Autoři:

Současné možnosti terapie osteoartrózy
Autoři: MUDr. Jakub Holešovský

Preferovaná úlevová léčba Asthma Bronchiale
Autoři: PharmDr. Petr Sedlák

Inhibitory karboanhydrázy v léčbě glaukomu
Autoři: MUDr. Petr Výborný, CSc., FEBO

Všechny kurzy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

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