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New functions for alpha-catenins in health and disease: from cancer to heart regeneration

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Abstract

Strong cell–cell adhesion mediated by adherens junctions is dependent on anchoring the transmembrane cadherin molecule to the underlying actin cytoskeleton. To do this, the cadherin cytoplasmic domain interacts with catenin proteins, which include α-catenin that binds directly to filamentous actin. Originally thought to be a static structure, the connection between the cadherin/catenin adhesion complex and the actin cytoskeleton is now considered to be dynamic and responsive to both intercellular and intracellular signals. Alpha-catenins are mechanosensing proteins that undergo conformational change in response to cytoskeletal tension thus modifying the linkage between the cadherin and the actin cytoskeleton. There are three α-catenin isoforms expressed in mouse and human: αE-catenin (CTNNA1), αN-catenin (CTNNA2) and αT-catenin (CTNNA3). This review summarizes recent progress in understanding the in vivo function(s) of α-catenins in tissue morphogenesis, homeostasis and disease. The role of α-catenin in the regulation of cellular proliferation will be discussed in the context of cancer and regeneration.

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References

  • Abe K, Chisaka O, van Roy F, Takeichi M (2004) Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat Neurosci 7:357–363

    Article  CAS  PubMed  Google Scholar 

  • Aoki K, Taketo MM (2007) Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J Cell Sci 120:3327–3335

    Article  CAS  PubMed  Google Scholar 

  • Barry ER, Camargo FD (2013) The Hippo superhighway: signaling crossroads converging on the Hippo/Yap pathway in stem cells and development. Curr Opin Cell Biol 25:247–253

    Article  CAS  PubMed  Google Scholar 

  • Barry AK, Tabdili H, Muhamed I, Wu J, Shashikanth N, Gomez GA, Yap AS, Gottardi CJ, de Rooij J, Wang N, Leckband DE (2014) alpha-catenin cytomechanics–role in cadherin-dependent adhesion and mechanotransduction. J Cell Sci 127:1779–1791

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bauce B, Nava A, Beffagna G, Basso C, Lorenzon A, Smaniotto G, de Bortoli M, Rigato I, Mazzotti E, Steriotis A, Marra MP, Towbin JA, Thiene G, Danieli GA, Rampazzo A (2010) Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm 7:22–29

    Article  PubMed  Google Scholar 

  • Bernstein DI, Kashon M, Lummus ZL, Johnson VJ, Fluharty K, Gautrin D, Malo JL, Cartier A, Boulet LP, Sastre J, Quirce S, Germolec D, Tarlo SM, Cruz MJ, Munoz X, Luster MI, Yucesoy B (2013) CTNNA3 (alpha-catenin) gene variants are associated with diisocyanate asthma: a replication study in a Caucasian worker population. Toxicol Sci 131:242–246

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Borrmann CM, Grund C, Kuhn C, Hofmann I, Pieperhoff S, Franke WW (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur J Cell Biol 85:469–485

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Lewis B, Moran A, Xie T (2012) Cadherin-mediated cell adhesion is critical for the closing of the mouse optic fissure. PLoS ONE 7:e51705

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Choi SH, Estaras C, Moresco JJ, Yates JR 3rd, Jones KA (2013) Alpha-Catenin interacts with APC to regulate beta-catenin proteolysis and transcriptional repression of Wnt target genes. Genes Dev 27:2473–2488

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cook SA, Bronson RT, Donahue LR, Ben-Arie N, Davisson MT (1997) Cerebellar deficient folia (cdf): a new mutation on mouse chromosome 6. Mamm Genome 8:108–112

    Article  CAS  PubMed  Google Scholar 

  • Dickinson DJ, Nelson WJ, Weis WI (2011) A polarized epithelium organized by beta- and alpha-catenin predates cadherin and metazoan origins. Science 331:1336–1339

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW, Harris CC, McLellan MD, Fulton RS, Fulton LL, Abbott RM, Hoog J, Dooling DJ, Koboldt DC, Schmidt H, Kalicki J, Zhang Q, Chen L, Lin L, Wendl MC, McMichael JF, Magrini VJ, Cook L, McGrath SD, Vickery TL, Appelbaum E, Deschryver K, Davies S, Guintoli T, Lin L, Crowder R, Tao Y, Snider JE, Smith SM, Dukes AF, Sanderson GE, Pohl CS, Delehaunty KD, Fronick CC, Pape KA, Reed JS, Robinson JS, Hodges JS, Schierding W, Dees ND, Shen D, Locke DP, Wiechert ME, Eldred JM, Peck JB, Oberkfell BJ, Lolofie JT, Du F, Hawkins AE, O’Laughlin MD, Bernard KE, Cunningham M, Elliott G, Mason MD, Thompson DM Jr, Ivanovich JL, Goodfellow PJ, Perou CM, Weinstock GM, Aft R, Watson M, Ley TJ, Wilson RK, Mardis ER (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464:999–1005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ertekin-Taner N, Ronald J, Asahara H, Younkin L, Hella M, Jain S, Gnida E, Younkin S, Fadale D, Ohyagi Y, Singleton A, Scanlin L, de Andrade M, Petersen R, Graff-Radford N, Hutton M, Younkin S (2003) Fine mapping of the alpha-T catenin gene to a quantitative trait locus on chromosome 10 in late-onset Alzheimer’s disease pedigrees. Hum Mol Genet 12:3133–3143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Fanjul-Fernandez M, Quesada V, Cabanillas R, Cadinanos J, Fontanil T, Obaya A, Ramsay AJ, Llorente JL, Astudillo A, Cal S, Lopez-Otin C (2013) Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently mutated in laryngeal carcinomas. Nat Commun 4:2531

    Article  PubMed  Google Scholar 

  • Folmsbee SS, Morales-Nebreda L, van Hengel J, Tyberghein K, van Roy F, Budinger GS, Bryce PJ, Gottardi CJ (2014) The cardiac protein alpha-T-catenin contributes to chemical-induced asthma. Am J Physiol Lung Cell Mol Physiol: Ajplung 00331:02014

    Google Scholar 

  • Forbes MS, Sperelakis N (1985) Intercalated discs of mammalian heart: a review of structure and function. Tissue Cell 17:605–648

    Article  CAS  PubMed  Google Scholar 

  • Franke WW, Borrmann CM, Grund C, Pieperhoff S (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol 85:69–82

    Article  CAS  PubMed  Google Scholar 

  • Fu CT, Zhu KY, Mi JQ, Liu YF, Murray ST, Fu YF, Ren CG, Dong ZW, Liu YJ, Dong M, Jin Y, Chen Y, Deng M, Zhang W, Chen B, Breslin P, Chen SJ, Chen Z, Becker MW, Zhu J, Zhang JW, Liu TX (2010) An evolutionarily conserved PTEN-C/EBPalpha-CTNNA1 axis controls myeloid development and transformation. Blood 115:4715–4724

    Article  CAS  PubMed  Google Scholar 

  • Goossens S, Janssens B, Bonne S, de Rycke R, Braet F, van Hengel J, van Roy F (2007a) A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs. J Cell Sci 120:2126–2136

    Article  CAS  PubMed  Google Scholar 

  • Goossens S, Janssens B, Vanpoucke G, de Rycke R, van Hengel J, van Roy F (2007b) Truncated isoform of mouse alphaT-catenin is testis-restricted in expression and function. FASEB J 21:647–655

    Article  CAS  PubMed  Google Scholar 

  • Halder G, Johnson RL (2011) Hippo signaling: growth control and beyond. Development 138:9–22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Halder G, Dupont S, Piccolo S (2012) Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat Rev Mol Cell Biol 13:591–600

    Article  CAS  PubMed  Google Scholar 

  • Hirschy A, Schatzmann F, Ehler E, Perriard JC (2006) Establishment of cardiac cytoarchitecture in the developing mouse heart. Dev Biol 289:430–441

    Article  CAS  PubMed  Google Scholar 

  • Hulpiau P, Gul IS, van Roy F (2013) New insights into the evolution of metazoan cadherins and catenins. Prog Mol Biol Transl Sci 116:71–94

    CAS  PubMed  Google Scholar 

  • Janssens B, Goossens S, Staes K, Gilbert B, van Hengel J, Colpaert C, Bruyneel E, Mareel M, van Roy F (2001) alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating strong cell-cell adhesion. J Cell Sci 114:3177–3188

    CAS  PubMed  Google Scholar 

  • Janssens B, Mohapatra B, Vatta M, Goossens S, Vanpoucke G, Kools P, Montoye T, van Hengel J, Bowles NE, van Roy F, Towbin JA (2003) Assessment of the CTNNA3 gene encoding human alpha T-catenin regarding its involvement in dilated cardiomyopathy. Hum Genet 112:227–236

    CAS  PubMed  Google Scholar 

  • Kim SH, Cho BY, Park CS, Shin ES, Cho EY, Yang EM, Kim CW, Hong CS, Lee JE, Park HS (2009) Alpha-T-catenin (CTNNA3) gene was identified as a risk variant for toluene diisocyanate-induced asthma by genome-wide association analysis. Clin Exp Allergy 39:203–212

    Article  CAS  PubMed  Google Scholar 

  • Kobielak A, Fuchs E (2004) Alpha-catenin: at the junction of intercellular adhesion and actin dynamics. Nat Rev Mol Cell Biol 5:614–625

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Larue L, Ohsugi M, Hirchenhain J, Kemler R (1994) E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proc Natl Acad Sci U S A 91:8263–8267

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Leerberg JM, Gomez GA, Verma S, Moussa EJ, Wu SK, Priya R, Hoffman BD, Grashoff C, Schwartz MA, Yap AS (2014) Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens. Curr Biol 24:1689–1699

    Article  CAS  PubMed  Google Scholar 

  • Li F, Wang X, Capasso JM, Gerdes AM (1996) Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 28:1737–1746

    Article  CAS  PubMed  Google Scholar 

  • Li J, Goossens S, van Hengel J, Gao E, Cheng L, Tyberghein K, Shang X, de Rycke R, van Roy F, Radice GL (2012) Loss of alphaT-catenin alters the hybrid adhering junctions in the heart and leads to dilated cardiomyopathy and ventricular arrhythmia following acute ischemia. J Cell Sci 125:1058–1067

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li J, Gao E, Vite A, Yi R, Gomez L, Goossens S, Roy F van and Radice G (2015) Alpha-catenins control cardiomyocyte proliferation by regulating Yap activity. Circ Res 116:70–79

  • Lien WH, Klezovitch O, Fernandez TE, Delrow J, Vasioukhin V (2006) alphaE-catenin controls cerebral cortical size by regulating the hedgehog signaling pathway. Science 311:1609–1612

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lincoln S, Allen M, Cox CL, Walker LP, Malphrus K, Qiu Y, Nguyen T, Rowley C, Kouri N, Crook J, Pankratz VS, Younkin S, Younkin L, Carrasquillo M, Zou F, Abdul-Hay SO, Springer W, Sando SB, Aasly JO, Barcikowska M, Wszolek ZK, Lewis JM, Dickson D, Graff-Radford NR, Petersen RC, Eckman E, Younkin SG, Ertekin-Taner N (2013) LRRTM3 interacts with APP and BACE1 and has variants associating with late-onset Alzheimer’s disease (LOAD). PLoS ONE 8:e64164

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu TX, Becker MW, Jelinek J, Wu WS, Deng M, Mikhalkevich N, Hsu K, Bloomfield CD, Stone RM, DeAngelo DJ, Galinsky IA, Issa JP, Clarke MF, Look AT (2007) Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Nat Med 13:78–83

    Article  PubMed  Google Scholar 

  • Maiden SL, Hardin J (2011) The secret life of alpha-catenin: moonlighting in morphogenesis. J Cell Biol 195:543–552

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Majercak J, Ray WJ, Espeseth A, Simon A, Shi XP, Wolffe C, Getty K, Marine S, Stec E, Ferrer M, Strulovici B, Bartz S, Gates A, Xu M, Huang Q, Ma L, Shughrue P, Burchard J, Colussi D, Pietrak B, Kahana J, Beher D, Rosahl T, Shearman M, Hazuda D, Sachs AB, Koblan KS, Seabrook GR, Stone DJ (2006) LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer’s disease. Proc Natl Acad Sci U S A 103:17967–17972

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • March HN, Rust AG, Wright NA, ten Hoeve J, de Ridder J, Eldridge M, van der Weyden L, Berns A, Gadiot J, Uren A, Kemp R, Arends MJ, Wessels LF, Winton DJ, Adams DJ (2011) Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis. Nat Genet 43:1202–1209

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Martin ER, Bronson PG, Li YJ, Wall N, Chung RH, Schmechel DE, Small G, Xu PT, Bartlett J, Schnetz-Boutaud N, Haines JL, Gilbert JR, Pericak-Vance MA (2005) Interaction between the alpha-T catenin gene (VR22) and APOE in Alzheimer’s disease. J Med Genet 42:787–792

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Matsushita T, Oyamada M, Fujimoto K, Yasuda Y, Masuda S, Wada Y, Oka T, Takamatsu T (1999) Remodeling of cell-cell and cell-extracellular matrix interactions at the border zone of rat myocardial infarcts. Circ Res 85:1046–1055

    Article  CAS  PubMed  Google Scholar 

  • Miyashita A, Arai H, Asada T, Imagawa M, Matsubara E, Shoji M, Higuchi S, Urakami K, Kakita A, Takahashi H, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R, D. Japanese Genetic Study Consortium for Alzeheimer’s (2007) Genetic association of CTNNA3 with late-onset Alzheimer’s disease in females. Hum Mol Genet 16:2854–2869

    Article  CAS  PubMed  Google Scholar 

  • Moleirinho S, Guerrant W, Kissil JL (2014) The Angiomotins–from discovery to function. FEBS Lett 588:2693–2703

    Article  CAS  PubMed  Google Scholar 

  • Mueller S, Rosenquist TA, Takai Y, Bronson RA, Wimmer E (2003) Loss of nectin-2 at Sertoli-spermatid junctions leads to male infertility and correlates with severe spermatozoan head and midpiece malformation, impaired binding to the zona pellucida, and oocyte penetration. Biol Reprod 69:1330–1340

    Article  CAS  PubMed  Google Scholar 

  • Myers A, Holmans P, Marshall H, Kwon J, Meyer D, Ramic D, Shears S, Booth J, DeVrieze FW, Crook R, Hamshere M, Abraham R, Tunstall N, Rice F, Carty S, Lillystone S, Kehoe P, Rudrasingham V, Jones L, Lovestone S, Perez-Tur J, Williams J, Owen MJ, Hardy J, Goate AM (2000) Susceptibility locus for Alzheimer’s disease on chromosome 10. Science 290:2304–2305

    Article  CAS  PubMed  Google Scholar 

  • Nagafuchi A, Takeichi M (1989) Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. Cell Regul 1:37–44

    PubMed Central  CAS  PubMed  Google Scholar 

  • Oxford EM, Musa H, Maass K, Coombs W, Taffet SM, Delmar M (2007) Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells. Circ Res 101:703–711

    Article  CAS  PubMed  Google Scholar 

  • Ozawa M, Baribault H, Kemler R (1989) The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J 8:1711–1717

    PubMed Central  CAS  PubMed  Google Scholar 

  • Park C, Falls W, Finger JH, Longo-Guess CM, Ackerman SL (2002) Deletion in Catna2, encoding alpha N-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation. Nat Genet 31:279–284

    CAS  PubMed  Google Scholar 

  • Perin P, Potocnik U (2014) Polymorphisms in recent GWA identified asthma genes CA10, SGK493, and CTNNA3 are associated with disease severity and treatment response in childhood asthma. Immunogenetics 66:143–151

    Article  CAS  PubMed  Google Scholar 

  • Peters NS, Green CR, Poole-Wilson PA, Severs NJ (1993) Reduced content of connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts. Circulation 88:864–875

    Article  CAS  PubMed  Google Scholar 

  • Peters NS, Coromilas J, Severs NJ, Wit AL (1997) Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation 95:988–996

    Article  CAS  PubMed  Google Scholar 

  • Piao HL, Yuan Y, Wang M, Sun Y, Liang H, Ma L (2014) alpha-catenin acts as a tumour suppressor in E-cadherin-negative basal-like breast cancer by inhibiting NF-kappaB signalling. Nat Cell Biol 16:245–254

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pieperhoff S, Franke WW (2007) The area composita of adhering junctions connecting heart muscle cells of vertebrates - IV: coalescence and amalgamation of desmosomal and adhaerens junction components - late processes in mammalian heart development. Eur J Cell Biol 86:377–391

    Article  CAS  PubMed  Google Scholar 

  • Pieperhoff S, Franke WW (2008) The area composita of adhering junctions connecting heart muscle cells of vertebrates. VI. Different precursor structures in non-mammalian species. Eur J Cell Biol 87:413–430

    Article  CAS  PubMed  Google Scholar 

  • Raftopoulos I, Davaris P, Karatzas G, Karayannacos P, Kouraklis G (1998) Level of alpha-catenin expression in colorectal cancer correlates with invasiveness, metastatic potential, and survival. J Surg Oncol 68:92–99

    Article  CAS  PubMed  Google Scholar 

  • Rampazzo A, Calore M, van Hengel J, van Roy F (2014) Intercalated discs and arrhythmogenic cardiomyopathy. Circ Cardiovasc Genet 7:930–940

    Article  PubMed  Google Scholar 

  • Sato PY, Musa H, Coombs W, Guerrero-Serna G, Patino GA, Taffet SM, Isom LL, Delmar M (2009) Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res 105:523–526

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sato PY, Coombs W, Lin X, Nekrasova O, Green KJ, Isom LL, Taffet SM, Delmar M (2011) Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res 109:193–201

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR, Camargo FD (2011) Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144:782–795

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schmid MT, Weinandy F, Wilsch-Brauninger M, Huttner WB, Cappello S, Gotz M (2014) The role of alpha-E-catenin in cerebral cortex development: radial glia specific effect on neuronal migration. Front Cell Neurosci 8:215

    Article  PubMed Central  PubMed  Google Scholar 

  • Sheikh F, Chen Y, Liang X, Hirschy A, Stenbit AE, Gu Y, Dalton ND, Yajima T, Lu Y, Knowlton KU, Peterson KL, Perriard JC, Chen J (2006) Alpha-E-catenin inactivation disrupts the cardiomyocyte adherens junction, resulting in cardiomyopathy and susceptibility to wall rupture. Circulation 114:1046–1055

    Article  CAS  PubMed  Google Scholar 

  • Shibata H, Takano H, Ito M, Shioya H, Hirota M, Matsumoto H, Kakudo Y, Ishioka C, Akiyama T, Kanegae Y, Saito I, Noda T (2007) Alpha-catenin is essential in intestinal adenoma formation. Proc Natl Acad Sci U S A 104:18199–18204

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Silvis MR, Kreger BT, Lien WH, Klezovitch O, Rudakova GM, Camargo FD, Lantz DM, Seykora JT and Vasioukhin V (2011) Alpha-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1. Sci Signal. 4:ra33

  • Soonpaa MH, Kim KK, Pajak L, Franklin M, Field LJ (1996) Cardiomyocyte DNA synthesis and binucleation during murine development. Am J Physiol 271:H2183–2189

    CAS  PubMed  Google Scholar 

  • Stocker AM and Chenn A (2006) Differential expression of alpha-E-catenin and alpha-N-catenin in the developing cerebral cortex. Brain Res 1073–1074:151–158

  • Swope D, Cheng L, Gao E, Li J, Radice GL (2012) Loss of cadherin-binding proteins beta-catenin and plakoglobin in the heart leads to gap junction remodeling and arrhythmogenesis. Mol Cell Biol 32:1056–1067

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Takeichi M, Abe K (2005) Synaptic contact dynamics controlled by cadherin and catenins. Trends Cell Biol 15:216–221

    Article  CAS  PubMed  Google Scholar 

  • Thiene G (2012) Arrhythmogenic cardiomyopathy: from autopsy to genes and transgenic mice (SCVP Achievement Award Lecture, San Antonio, TX, February 27, 2011). Cardiovasc Pathol 21:229–239

    Article  PubMed  Google Scholar 

  • Thomas WA, Boscher C, Chu YS, Cuvelier D, Martinez-Rico C, Seddiki R, Heysch J, Ladoux B, Thiery JP, Mege RM, Dufour S (2013) Alpha-Catenin and vinculin cooperate to promote high E-cadherin-based adhesion strength. J Biol Chem 288:4957–4969

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M (2002) Cadherin regulates dendritic spine morphogenesis. Neuron 35:77–89

    Article  CAS  PubMed  Google Scholar 

  • Torres M, Stoykova A, Huber O, Chowdhury K, Bonaldo P, Mansouri A, Butz S, Kemler R, Gruss P (1997) An alpha-E-catenin gene trap mutation defines its function in preimplantation development. Proc Natl Acad Sci U S A 94:901–906

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tyberghein K, Goossens S, Haigh JJ, van Roy F, van Hengel J (2012) Tissue-wide overexpression of alpha-T-catenin results in aberrant trophoblast invasion but does not cause embryonic mortality in mice. Placenta 33:554–560

    Article  CAS  PubMed  Google Scholar 

  • Uemura M, Takeichi M (2006) Alpha N-catenin deficiency causes defects in axon migration and nuclear organization in restricted regions of the mouse brain. Dev Dyn 235:2559–2566

    Article  CAS  PubMed  Google Scholar 

  • van den Borne SW, Narula J, Voncken JW, Lijnen PM, Vervoort-Peters HT, Dahlmans VE, Smits JF, Daemen MJ, Blankesteijn WM (2008) Defective intercellular adhesion complex in myocardium predisposes to infarct rupture in humans. J Am Coll Cardiol 51:2184–2192

    Article  PubMed  Google Scholar 

  • van Dijk M, van Bezu J, van Abel D, Dunk C, Blankenstein MA, Oudejans CB, Lye SJ (2010) The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation. Hum Mol Genet 19:2658–2667

    Article  PubMed  Google Scholar 

  • van Hengel J, Calore M, Bauce B, Dazzo E, Mazzotti E, de Bortoli M, Lorenzon A, Li Mura IE, Beffagna G, Rigato I, Vleeschouwers M, Tyberghein K, Hulpiau P, van Hamme E, Zaglia T, Corrado D, Basso C, Thiene G, Daliento L, Nava A, van Roy F, Rampazzo A (2013) Mutations in the area composita protein alphaT-catenin are associated with arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 34:201–210

    Article  PubMed  Google Scholar 

  • Vanpoucke G, Goossens S, de Craene B, Gilbert B, van Roy F, Berx G (2004) GATA-4 and MEF2C transcription factors control the tissue-specific expression of the alphaT-catenin gene CTNNA3. Nucleic Acids Res 32:4155–4165

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vasioukhin V, Bauer C, Degenstein L, Wise B, Fuchs E (2001) Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell 104:605–617

    Article  CAS  PubMed  Google Scholar 

  • Vermeulen SJ, Bruyneel EA, Bracke ME, de Bruyne GK, Vennekens KM, Vleminckx KL, Berx GJ, van Roy FM, Mareel MM (1995) Transition from the noninvasive to the invasive phenotype and loss of alpha-catenin in human colon cancer cells. Cancer Res 55:4722–4728

    CAS  PubMed  Google Scholar 

  • Vermeulen SJ, Nollet F, Teugels E, Vennekens KM, Malfait F, Philippe J, Speleman F, Bracke ME, van Roy FM, Mareel MM (1999) The alphaE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. Oncogene 18:905–915

    Article  CAS  PubMed  Google Scholar 

  • Xu T, Yang Z, Vatta M, Rampazzo A, Beffagna G, Pilichou K, Scherer SE, Saffitz J, Kravitz J, Zareba W, Danieli GA, Lorenzon A, Nava A, Bauce B, Thiene G, Basso C, Calkins H, Gear K, Marcus F, Towbin JA, I. Multidisciplinary Study of Right Ventricular Dysplasia (2010) Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol 55:587–597

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yonemura S, Wada Y, Watanabe T, Nagafuchi A, Shibata M (2010) Alpha-Catenin as a tension transducer that induces adherens junction development. Nat Cell Biol 12:533–542

    Article  CAS  PubMed  Google Scholar 

  • Zemljic-Harpf AE, Miller JC, Henderson SA, Wright AT, Manso AM, Elsherif L, Dalton ND, Thor AK, Perkins GA, McCulloch AD, Ross RS (2007) Cardiac-myocyte-specific excision of the vinculin gene disrupts cellular junctions, causing sudden death or dilated cardiomyopathy. Mol Cell Biol 27:7522–7537

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao ZM, Reynolds AB, Gaucher EA (2011) The evolutionary history of the catenin gene family during metazoan evolution. BMC Evol Biol 11:198

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We thank Frans van Roy for sharing unpublished data. We thank Jennifer Wilson for editorial assistance. Work in the authors’ laboratory is supported by the National Institutes of Health (HL111788, CA176097 to G.R.).

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  1. Department of Medicine, Center for Translational Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Suite 543E Jefferson Alumni Hall, 1020 Locust St., Philadelphia, PA, 19107, USA

    Alexia Vite, Jifen Li & Glenn L. Radice

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  1. Alexia Vite
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  2. Jifen Li
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Correspondence to Glenn L. Radice.

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Vite, A., Li, J. & Radice, G.L. New functions for alpha-catenins in health and disease: from cancer to heart regeneration. Cell Tissue Res 360, 773–783 (2015). https://doi.org/10.1007/s00441-015-2123-x

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  • DOI: https://doi.org/10.1007/s00441-015-2123-x

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