Abstract
Cell competition is an important surveillance mechanism that measures relative fitness between cells in a tissue during development, homeostasis, and disease. Specifically, cells that are “less fit” (losers) are actively eliminated by relatively “more fit” (winners) neighbours, despite the less fit cells otherwise being able to survive in a genetically uniform tissue. Originally described in the epithelial tissues of Drosophila larval imaginal discs, cell competition has since been shown to occur in other epithelial and non-epithelial Drosophila tissues, as well as in mammalian model systems. Many genes and signalling pathways have been identified as playing conserved roles in the mechanisms of cell competition. Among them are genes required for the establishment and maintenance of apico-basal cell polarity: the Crumbs/Stardust/Patj (Crb/Sdt/Patj), Bazooka/Par-6/atypical Protein Kinase C (Baz/Par-6/aPKC), and Scribbled/Discs large 1/Lethal (2) giant larvae (Scrib/Dlg1/L(2)gl) modules. In this chapter, we describe the concepts and mechanisms of cell competition, with emphasis on the relationship between cell polarity proteins and cell competition, particularly the Scrib/Dlg1/L(2)gl module, since this is the best described module in this emerging field.
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References
Abrams JM (2002) Competition and compensation: coupled to death in development and cancer. Cell 110:403–406
Agrawal N, Joshi S, Kango M, Saha D, Mishra A, Sinha P (1995) Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: growth and pattern formation in genetic mosaics. Dev Biol 169:387–398
Alpar L, Bergantiños C, Johnston LA (2018) Spatially restricted regulation of Spätzle/toll signaling during cell competition. Dev Cell 46:706–719
Andersen DS, Colombani J, Palmerini V, Chakrabandhu K, Boone E, Röthlisberger M, Toggweiler J, Basler K, Mapelli M, Hueber A-O, Léopold P (2015) The Drosophila TNF receptor Grindelwald couples loss of cell polarity and neoplastic growth. Nature 522:482–486
Archibald A, Al-Masri M, Liew-Spilger A, McCaffrey L (2015) Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling. Mol Biol Cell 26:3578–3595
Baker NE (2017) Mechanisms of cell competition emerging from Drosophila studies. Curr Opin Cell Biol 48:40–46
Ballesteros-Arias L, Saavedra V, Morata G (2013) Cell competition may function either as tumour-suppressing or as tumour-stimulating factor in Drosophila. Oncogene 33:4377–4384
Bilder D (2004) Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors. Genes Dev 18:1909–1925
Bilder D, Li M, Perrimon N (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289:113–116
Bondar T, Medzhitov R (2010) p53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell 6:309–322
Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the Proapoptotic gene hid in Drosophila. Cell 113:25–36
Brose K, Tessier-Lavigne M (2000) Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr Opin Neurobiol 10:95–102
Brumby AM, Richardson HE (2003) scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J 22:5769
Bunker BD, Nellimoottil TT, Boileau RM, Classen AK, Bilder D (2015) The transcriptional response to tumorigenic polarity loss in Drosophila. elife 4:e03189
Cao F, Miao Y, Xu K, Liu P (2015) Lethal (2) Giant larvae: an indispensable regulator of cell polarity and Cancer development. Int J Biol Sci 11:380–389
Caria S, Magtoto CM, Samiei T, Portela M, Lim KYB, How JY, Stewart BZ, Humbert PO, Richardson HE, Kvansakul M (2018) Drosophila melanogaster Guk-holder interacts with the scribbled PDZ1 domain and regulates epithelial development with scribbled and discs large. J Biol Chem 293:4519–4531
Casas-Tintó S, Ferrús A (under review) Troponin-I localizes selected apico-basal cell polarity signals. bioRxiv, pp 1–9
Casas-Tintó S, Lolo F-N, Moreno E (2015) Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA synthetase by loser cells recruits haemocytes during cell competition. Nat Commun 6:1–12
Casas-Tintó S, Maraver A, Serrano M, Ferrús A (2016) Troponin-I enhances and is required for oncogenic overgrowth. Oncotarget 7:52631–52642
Chen C-L, Gajewski KM, Hamaratoglu F, Bossuyt W, Sansores-Garcia L, Tao C, Halder G (2010) The apical-basal cell polarity determinant crumbs regulates hippo signaling in Drosophila. Proc Natl Acad Sci U S A 107:15810–15815
Chen CL, Schroeder MC, Kango-Singh M, Tao C, Halder G (2012) Tumor suppression by cell competition through regulation of the hippo pathway. Proc Natl Acad Sci U S A 109:484–489
Clavería C, Giovinazzo G, Sierra R, Torres M (2013) Myc-driven endogenous cell competition in the early mammalian embryo. Nature 500:39–44
Clavería C, Torres M (2016) Cell competition: mechanisms and physiological roles. Annu Rev Cell Dev Biol 32:411–439
Cordero JB, Macagno JP, Stefanatos RK, Strathdee KE, Cagan RL, Vidal M (2010) Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev Cell 18:999–1011
de la Cova C, Abril M, Bellosta P, Gallant P, Johnston LA (2004) Drosophila Myc regulates organ size by inducing cell competition. Cell 117:107–116
de la Cova C, Johnston LA (2006) Myc in model organisms: a view from the flyroom. Semin Cancer Biol 16:303–312
de la Cova C, Senoo-Matsuda N, Ziosi M, Wu DC, Bellosta P, Quinzii CM, Johnston LA (2014) Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability. Cell Metab 19:470–483
de Vreede G, Morrison HA, Houser AM, Boileau RM, Andersen DS, Colombani J, Bilder D (2018) A Drosophila tumor suppressor gene prevents tonic TNF signaling through receptor N-glycosylation. Dev Cell 45:595–605
Di Giacomo S, Sollazzo M, de Biase D, Ragazzi M, Bellosta P, Pession A, Grifoni D (2017a) Human cancer cells signal their competitive fitness through MYC activity. Sci Rep 7:1–12
Di Giacomo S, Sollazzo M, Paglia S, Grifoni D (2017b) MYC, cell competition, and cell death in cancer: the inseparable triad. Genes (Basel) 8:1–11
Díaz-Díaz C, Fernandez de Manuel L, Jimenez-Carretero D, Montoya MC, Clavería C, Torres M (2017) Pluripotency surveillance by Myc-driven competitive elimination of differentiating cells. Dev Cell 42:585–599
Doggett K, Grusche FA, Richardson HE, Brumby AM (2011) Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling. BMC Dev Biol:11, 57
Dow LE, Elsum IA, King CL, Kinross KM, Richardson HE, Humbert PO (2008) Loss of human scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling. Oncogene 27:5988–6001
Eichenlaub T, Cohen SM, Herranz H (2016) Cell competition drives the formation of metastatic tumors in a Drosophila model of epithelial tumor formation. Curr Biol 26:419–427
Elsum IA, Yates LL, Pearson HB, Phesse TJ, Long F, O’Donoghue R, Ernst M, Cullinane C, Humbert PO (2013) Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo. Oncogene 33:5523–5533
Enomoto M, Igaki T (2013) Src controls tumorigenesis via JNK-dependent regulation of the hippo pathway in Drosopihla. EMBO Rep 14:65–72
Enomoto M, Siow C, Igaki T (2018) Drosophila as a Cancer model. In: Yamaguchi M (ed) Drosophila models for human diseases. Springer Singapore, Singapore, pp 173–194
Feigin ME, Akshinthala SD, Araki K, Rosenberg AZ, Muthuswamy LB, Martin B, Lehmann BD, Berman HK, Pietenpol JA, Cardiff RD, Muthuswamy SK (2014) Mislocalization of the cell polarity protein scribble promotes mammary tumorigenesis and is associated with basal breast Cancer. Cancer Res 74:3180–3194
Fletcher GC, Lucas EP, Brain R, Tournier A, Thompson BJ (2012) Positive feedback and mutual antagonism combine to polarize crumbs in the Drosophila follicle cell epithelium. Curr Biol 22:1116–1122
Froldi F, Ziosi M, Garoia F, Pession A, Grzeschik NA, Bellosta P, Strand D, Richardson HE, Pession A, Grifoni D (2010) The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol 8:33
Gateff E (1978) Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200:1448–1459
Germani F, Hain D, Sternlicht D, Moreno E, Basler K (2018) The toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner. elife 7:e39939
Gödde NJ, Pearson HB, Smith LK, Humbert PO (2014a) Dissecting the role of polarity regulators in cancer through the use of mouse models. Exp Cell Res 328:249–257
Gödde NJ, Sheridan JM, Smith LK, Pearson HB, Britt KL, Galea RC, Yates LL, Visvader JE, Humbert PO (2014b) Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland. PLoS Genet 10:e1004323
Govind S (2008) Innate immunity in Drosophila: pathogens and pathways. Insect Science 15:29–43
Grzeschik NA, Amin N, Secombe J, Brumby AM, Richardson HE (2007) Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye. Dev Biol 311:106–123
Grzeschik NA, Parsons LM, Allott ML, Harvey KF, Richardson HE (2010) Lgl, aPKC, and crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol 20:573–581
Hafezi Y, Bosch JA, Hariharan IK (2012) Differences in levels of the transmembrane protein crumbs can influence cell survival at clonal boundaries. Dev Biol 368:358–369
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
Harvey KF, Pfleger CM, Hariharan IK (2003) The Drosophila Mst Ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell 114:457–467
Hogan C, Dupré-Crochet S, Norman M, Kajita M, Zimmermann C, Pelling AE, Piddini E, Baena-López LA, Vincent J-P, Itoh Y, Hosoya H, Pichaud F, Fujita Y (2009) Characterization of the interface between normal and transformed epithelial cells. Nat Cell Biol 11:460–467
Humbert PO, Grzeschik NA, Brumby AM, Galea R, Elsum I, Richardson HE (2008) Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module. Oncogene 27:6888–6907
Humbert PO, Russell SM, Smith L, Richardson HE (2015) The scribble–Dlg–Lgl module in cell polarity regulation. In: Cell Polarity 1, chapter 4. Springer, Cham, pp 65–111
Igaki T, Kanda H, Yamamoto-Goto Y, Kanuka H, Kuranaga E, Aigaki T, Miura M (2002) Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J 21:3009
Igaki T, Pagliarini RA, Xu T (2006) Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol 16:1139–1146
Igaki T, Pastor-Pareja JC, Aonuma H, Miura M, Xu T (2009) Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. Dev Cell 16:458–465
Johnston LA, Prober DA, Edgar BA, Eisenman RN, Gallant P (1999) Drosophila myc regulates cellular growth during development. Cell 98:779–790
Kajita M, Fujita Y (2015) EDAC: epithelial defence against cancer—cell competition between normal and transformed epithelial cells in mammals. The Journal of Biochemistry 158:15–23
Kajita M, Hogan C, Harris AR, Dupre-Crochet S, Itasaki N, Kawakami K, Charras G, Tada M, Fujita Y (2010) Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells. J Cell Sci 123:171–180
Kale A, Li W, Lee CH, Baker NE (2015) Apoptotic mechanisms during competition of ribosomal protein mutant cells: roles of the initiator caspases Dronc and dream/Strica. Cell Death Differ 22:1300–1312
Kapil S, Sharma BK, Patil M, Elattar S, Yuan J, Hou SX, Kolhe R, Satyanarayana A (2017) The cell polarity protein Scrib functions as a tumor suppressor in liver cancer. Oncotarget 8:26515–26531
Katsukawa M, Ohsawa S, Zhang L, Yan Y, Igaki T (2018) Serpin facilitates tumor-suppressive cell competition by blocking toll-mediated Yki activation in Drosophila. Curr Biol 28:1756–1767
Kon S, Ishibashi K, Katoh H, Kitamoto S, Shirai T, Tanaka S, Kajita M, Ishikawa S, Yamauchi H, Yako Y, Kamasaki T, Matsumoto T, Watanabe H, Egami R, Sasaki A, Nishikawa A, Kameda I, Maruyama T, Narumi R, Morita T, Sasaki Y, Enoki R, Honma S, Imamura H, Oshima M, Soga T, Miyazaki J, Duchen MR, Nam J-M, Onodera Y, Yoshioka S, Kikuta J, Ishii M, Imajo M, Nishida E, Fujioka Y, Ohba Y, Sato T, Fujita Y (2017) Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes. Nat Cell Biol 19:530–541
Kongsuwan K, Yu Q, Vincent A, Frisardi MC, Rosbash M, Lengyel JA, Merriam J (1985) A Drosophila Minute gene encodes a ribosomal protein. Nature 317:555–558
La Fortezza M, Schenk M, Cosolo A, Kolybaba A, Grass I, Classen AK (2016) JAK/STAT signalling mediates cell survival in response to tissue stress. Development 143:2907–2919
Leong GR, Goulding KR, Amin N, Richardson HE, Brumby AM (2009) scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs. BMC Biol 7:62
Levayer R, Dupont C, Moreno E (2016) Tissue crowding induces caspase-dependent competition for space. Curr Biol 26:670–677
Ling C, Zheng Y, Yin F, Yu J, Huang J, Hong Y, Wu S, Pan D (2010) The apical transmembrane protein crumbs functions as a tumor suppressor that regulates hippo signaling by binding to expanded. Proc Natl Acad Sci U S A 107:10532–10537
Lolo F-N, Casas-Tintó S, Moreno E (2012) Cell competition time line: winners kill losers, which are extruded and engulfed by Hemocytes. Cell Rep 2:526–539
Lolo F-N, Tintó SC, Moreno E (2013) How winner cells cause the demise of loser cells. BioEssays 35:348–353
Lu H, Bilder D (2005) Endocytic control of epithelial polarity and proliferation in Drosophila. Nat Cell Biol 7:1232–1239
Ma X, Chen Y, Zhang S, Xu W, Shao Y, Yang Y, Li W, Li M, Xue L (2016) Rho1–Wnd signaling regulates loss-of-cell polarity-induced cell invasion in Drosophila. Oncogene 35:846–855
Ma X, Guo X, Richardson HE, Xu T, Xue L (2018) POSH regulates hippo signaling through ubiquitin-mediated expanded degradation. Proc Natl Acad Sci U S A 115:2150–2155
Madan E, Gogna R, Moreno E (2018) Cell competition in development: information from flies and vertebrates. Curr Opin Cell Biol 55:150–157
Mamada H, Sato T, Ota M, Sasaki H (2015) Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the activity of Tead family proteins and Myc. J Cell Sci 128:790–803
Marinari E, Mehonic A, Curran S, Gale J, Duke T, Baum B (2012) Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature 484:542–545
Martins VC, Busch K, Juraeva D, Blum C, Ludwig C, Rasche V, Lasitschka F, Mastitsky SE, Brors B, Hielscher T, Fehling HJ, Rodewald H-R (2014) Cell competition is a tumour suppressor mechanism in the thymus. Nature 509:465–470
Marygold SJ, Roote J, Reuter G, Lambertsson A, Ashburner M, Millburn GH, Harrison PM, Yu Z, Kenmochi N, Kaufman TC, Leevers SJ, Cook KR (2007) The ribosomal protein genes and Minute loci of Drosophila melanogaster. Genome Biol 8:R216
Mathew D, Gramates LS, Packard M, Thomas U, Bilder D, Perrimon N, Gorczyca M, Budnik V (2002) Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Curr Biol 12:531–539
Menendez J, Perez-Garijo A, Calleja M, Morata G (2010) A tumor-suppressing mechanism in Drosophila involving cell competition and the hippo pathway. Proc Natl Acad Sci U S A 107:14651–14656
Menut L, Vaccari T, Dionne H, Hill J, Wu G, Bilder D (2007) A mosaic genetic screen for Drosophila neoplastic tumor suppressor genes based on defective pupation. Genetics 177:1667–1677
Merino MM, Levayer R, Moreno E (2016) Survival of the fittest: essential roles of cell competition in development, aging, and Cancer. Trends Cell Biol 26:776–788
Merino MM, Rhiner C, López-Gay JM, Buechel D, Hauert B, Moreno E (2015) Elimination of unfit cells maintains tissue health and prolongs lifespan. Cell 160:461–476
Merino MM, Rhiner C, Portela M, Moreno E (2013) “Fitness fingerprints” mediate physiological culling of unwanted neurons in Drosophila. Curr Biol 23:1300–1309
Meyer SN, Amoyel M, Bergantinos C, de la Cova C, Schertel C, Basler K, Johnston LA (2014) An ancient defense system eliminates unfit cells from developing tissues during cell competition. Science 346:1258236
Misra JR, Irvine KD (2018) The hippo signaling network and its biological functions. Annu Rev Genet 52:65–87
Moberg KH, Schelble S, Burdick SK, Hariharan IK (2005) Mutations in erupted, the Drosophila Ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev Cell 9:699–710
Morata G, Ripoll P (1975) Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev Biol 42:211–221
Moreno E, Basler K (2004) dMyc transforms cells into super-competitors. Cell 117:117–129
Moreno E, Basler K, Morata G (2002a) Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416:755–759
Moreno E, Yan M, Basler K (2002b) Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily. Curr Biol 12:1263–1268
Muthuswamy SK, Xue B (2012) Cell polarity as a regulator of Cancer cell behavior plasticity. Annu Rev Cell Dev Biol 28:599–625
Muzzopappa M, Murcia L, Milán M (2017) Feedback amplification loop drives malignant growth in epithelial tissues. Proc Natl Acad Sci U S A 114:7291–7300
Nahvi A, Shoemaker CJ, Green R (2009) An expanded seed sequence definition accounts for full regulation of the hid 3′ UTR by bantam miRNA. RNA (New York, NY) 15:814–822
Neto-Silva RM, de Beco S, Johnston LA (2010) Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of yap. Dev Cell 19:507–520
Norman M, Wisniewska KA, Lawrenson K, Garcia-Miranda P, Tada M, Kajita M, Mano H, Ishikawa S, Ikegawa M, Shimada T, Fujita Y (2012) Loss of scribble causes cell competition in mammalian cells. J Cell Sci 125:59–66
Oertel M, Menthena A, Dabeva MD, Shafritz DA (2006) Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology 130:507–520
Oh H, Irvine KD (2010) Yorkie: the final destination of hippo signaling. Trends Cell Biol 20:410–417
Ohsawa S, Sugimura K, Takino K, Xu T, Miyawaki A, Igaki T (2011) Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev Cell 20:315–328
Ohshiro T, Yagami T, Zhang C, Matsuzaki F (2000) Role of cortical tumour-suppressor proteins in asymmetric division of Drosophila neuroblast. Nature 408:593–596
Oliver ER, Saunders TL, Tarle SA, Glaser T (2004) Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131:3907–3920
Pagliarini RA, Xu T (2003) A genetic screen in Drosophila for metastatic behavior. Science 302:1227–1231
Parsons LM, Portela M, Grzeschik NA, Richardson HE (2014) Lgl regulates notch signaling via endocytosis, independently of the apical aPKC-Par6-Baz polarity complex. Curr Biol 24:2073–2084
Pearson HB, McGlinn E, Phesse TJ, Schlüter H, Srikumar A, Gödde NJ, Woelwer CB, Ryan A, Phillips WA, Ernst M, Kaur P, Humbert PO (2015) The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. Mol Cancer 14:169
Pearson HB, Perez-Mancera PA, Dow LE, Ryan A, Tennstedt P, Bogani D, Elsum IA, Greenfield A, Tuveson DA, Simon R, Humbert PO (2011) SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J Clin Invest 121:4257–4267
Peng C-Y, Manning L, Albertson R, Doe CQ (2000) The tumour-suppressor genes lgl and dlg regulate basal protein targeting in Drosophila neuroblasts. Nature 408:596–600
Portela M, Casas-Tinto S, Rhiner C, López-Gay JM, Domínguez O, Soldini D, Moreno E (2010) Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev Cell 19:562–573
Rejon C, Al-Masri M, McCaffrey L (2016) Cell polarity proteins in breast Cancer progression. J Cell Biochem 117:2215–2223
Rhiner C, López-Gay JM, Soldini D, Casas-Tinto S, Martín FA, Lombardía L, Moreno E (2010) Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev Cell 18:985–998
Ribeiro P, Holder M, Frith D, Snijders AP, Tapon N (2014) Crumbs promotes expanded recognition and degradation by the SCFSlimb/β-TrCP ubiquitin ligase. Proc Natl Acad Sci U S A 111:1980–1989
Richardson HE, Portela M (2016) Robo-enabled tumor cell extrusion. Dev Cell 39:629–631
Richardson HE, Portela M (2018) Modelling cooperative tumorigenesis in Drosophila. Biomed Res Int 2018, pp 1–29
Rives-Quinto N, Franco M, de Torres-Jurado A, Carmena A (2017) Synergism between canoe and scribble mutations causes tumor-like overgrowth via Ras activation in neural stem cells and epithelia. Development 144:2570–2583
Robinson BS, Huang J, Hong Y, Moberg KH (2010) Crumbs regulates Salvador/warts/hippo signaling in Drosophila via the FERM-domain protein expanded. Curr Biol 20:582–590
Rodrigues AB, Zoranovic T, Ayala-Camargo A, Grewal S, Reyes-Robles T, Krasny M, Wu DC, Johnston LA, Bach EA (2012) Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, wingless and ribosome biogenesis. Development 139:4051–4061
Sakakibara J, Sakakibara M, Shiina N, Fujimori T, Okubo Y, Fujisaki K, Nagashima T, Sangai T, Nakatani Y, Miyazaki M (2017) Expression of cell polarity protein scribble differently affects prognosis in primary tumor and lymph node metastasis of breast cancer patients. Breast Cancer 24:393–399
Sancho M, Di-Gregorio A, George N, Pozzi S, Sanchez JM, Pernaute B, Rodriguez TA (2013) Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation. Dev Cell 26:19–30
Schroeder MC, Chen CL, Gajewski K, Halder G (2012) A non-cell-autonomous tumor suppressor role for Stat in eliminating oncogenic scribble cells. Oncogene 32:4471–4479
Shlevkov E, Morata G (2011) A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila. Cell Death Differ 19:451–460
Shraiman BI (2005) Mechanical feedback as a possible regulator of tissue growth. Proc Natl Acad Sci U S A 102:3318–3323
Simpson P (1979) Parameters of cell competition in the compartments of the wing disc of Drosophila. Dev Biol 69:182–193
Simpson P, Morata G (1981) Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. Dev Biol 85:299–308
Sollazzo M, Genchi C, Paglia S, Di Giacomo S, Pession A, de Biase D, Grifoni D (2018) High MYC levels favour multifocal carcinogenesis. Front Genet 9:1–15
Sotillos S, Díaz-Meco MT, Caminero E, Moscat J, Campuzano S (2004) DaPKC-dependent phosphorylation of crumbs is required for epithelial cell polarity in Drosophila. J Cell Biol 166:549–557
Suijkerbuijk SJ, Kolahgar G, Kucinski I, Piddini E (2016) Cell competition drives the growth of intestinal adenomas in Drosophila. Curr Biol 26:428–438
Sun G, Irvine KD (2013) Ajuba family proteins link JNK to hippo signaling. Sci Signal 6:ra81
Tamori Y, Bialucha CU, Tian A-G, Kajita M, Huang Y-C, Norman M, Harrison N, Poulton J, Ivanovitch K, Disch L, Liu T, Deng W-M, Fujita Y (2010) Involvement of Lgl and mahjong/VprBP in cell competition. PLoS Biol 8:1–10
Tapon N, Harvey KF, Bell DW, Wahrer DCR, Schiripo TA, Haber DA, Hariharan IK (2002) salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human Cancer cell lines. Cell 110:467–478
Tepass U (2012) The apical polarity protein network in Drosophila epithelial cells: regulation of polarity, junctions, morphogenesis, cell growth, and survival. Annu Rev Cell Dev Biol 28:655–685
Tepass U, Theres C, Knust E (1990) crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61:787–799
Thiery JP (2002) Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454
Thompson BJ, Mathieu J, Sung H-H, Loeser E, Rørth P, Cohen SM (2005) Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev Cell 9:711–720
Tyler DM, Li W, Zhuo N, Pellock B, Baker NE (2007) Genes affecting cell competition in Drosophila. Genetics 175:643–657
Uhlirova M, Jasper H, Bohmann D (2005) Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. Proc Natl Acad Sci U S A 102:13123–13128
Vaccari T, Bilder D (2005) The Drosophila tumor suppressor vps25 prevents nonautonomous Overproliferation by regulating notch trafficking. Dev Cell 9:687–698
Valanne S, Wang J-H, Rämet M (2011) The Drosophila toll signaling pathway. J Immunol 186:649–656
Vaughen J, Igaki T (2016) Slit-Robo repulsive signaling extrudes tumorigenic cells from epithelia. Dev Cell 39:683–695
Vidal M (2010) The dark side of fly TNF. Cell Cycle 9:3851–3856
Vidal M, Larson DE, Cagan RL (2006) Csk-deficient boundary cells are eliminated from Normal Drosophila epithelia by exclusion, migration, and apoptosis. Dev Cell 10:33–44
Villa Del Campo C, Claveria C, Sierra R, Torres M (2014) Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart. Cell Rep 8:1741–1751
Vincent J-P, Fletcher AG, Baena-Lopez LA (2013) Mechanisms and mechanics of cell competition in epithelia. Nat Rev Mol Cell Biol 14:581–591
Vincent JP, Kolahgar G, Gagliardi M, Piddini E (2011) Steep differences in wingless signaling trigger Myc-independent competitive cell interactions. Dev Cell 21:366–374
Wagstaff L, Goschorska M, Kozyrska K, Duclos G, Kucinski I, Chessel A, Hampton-O’Neil L, Bradshaw CR, Allen GE, Rawlins EL, Silberzan P, Carazo Salas RE, Piddini E (2016) Mechanical cell competition kills cells via induction of lethal p53 levels. Nat Commun 7:1–14
Wodarz A (2000) Tumor suppressors: linking cell polarity and growth control. Curr Biol 10:624–626
Wu M, Pastor-Pareja JC, Xu T (2010) Interaction between RasV12 and scribbled clones induces tumour growth and invasion. Nature 463:545–548
Yamamoto M, Ohsawa S, Kunimasa K, Igaki T (2017) The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition. Nature 542:246–250
Yamashita K, Ide M, Furukawa KT, Suzuki A, Hirano H, Ohno S (2015) Tumor suppressor protein Lgl mediates G1 cell cycle arrest at high cell density by forming an Lgl-VprBP-DDB1 complex. Mol Biol Cell 26:2426–2438
Zhang S, Feng Y, Narayan O, Zhao L-J (2001) Cytoplasmic retention of HIV-1 regulatory protein Vpr by protein-protein interaction with a novel human cytoplasmic protein VprBP. Gene 263:131–140
Ziosi M, Baena-López LA, Grifoni D, Froldi F, Pession A, Garoia F, Trotta V, Bellosta P, Cavicchi S, Pession A (2010) dMyc functions downstream of Yorkie to promote the Supercompetitive behavior of hippo pathway mutant cells. PLoS Genet 6:e1001140
Zoranovic T, Grmai L, Bach EA (2013) Regulation of proliferation, cell competition, and cellular growth by the Drosophila JAK-STAT pathway. JAK-STAT 2:e25408
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JELM is supported by Australian Research Council (Grant DP170102549), NFL is supported by a La Trobe University PhD student scholarship, and HER is supported by funds from the School for Molecular Science at La Trobe University.
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Fahey-Lozano, N., La Marca, J.E., Portela, M., Richardson, H.E. (2019). Drosophila Models of Cell Polarity and Cell Competition in Tumourigenesis. In: Deng, WM. (eds) The Drosophila Model in Cancer. Advances in Experimental Medicine and Biology, vol 1167. Springer, Cham. https://doi.org/10.1007/978-3-030-23629-8_3
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