Abstract
Adherens junctions, which are intercellular adhesive complexes that are crucial for maintaining epithelial homeostasis, are downregulated in many cancers to promote tumour progression. However, the role of desmosomes — adhesion complexes that are related to adherens junctions — in carcinogenesis has remained elusive. Recent studies using mouse genetic approaches have uncovered a role for desmosomes in tumour suppression, demonstrating that desmosome downregulation occurs before that of adherens junctions to drive tumour development and early invasion, suggesting a two-step model of adhesion dysfunction in cancer progression.
Access options
Subscribe to Journal
Get full journal access for 1 year
$265.00
only $22.08 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
from$8.99
All prices are NET prices.
References
- 1.
Cooper, G. M. Oncogenes (Jones and Barlett Publishers, Boston, 1995).
- 2.
Schock, F. & Perrimon, N. Molecular mechanisms of epithelial morphogenesis. Annu. Rev. Cell Dev. Biol. 18, 463–493 (2002).
- 3.
Jamora, C. & Fuchs, E. Intercellular adhesion, signalling and the cytoskeleton. Nature Cell Biol. 4, e101–e108 (2002).
- 4.
Simpson, C. L. & Green, K. J. Desmosomes: new perspectives on a classic. J. Invest. Dermatol. 127, 2499–2515 (2007).
- 5.
Vasioukhin, V., Bauer, C., Yin, M. & Fuchs, E. Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100, 209–219 (2000).
- 6.
Chen, C. P., Psoy, S., Ben-Shaul, A., Shapiro, L. & Honig, B. H. Specificity of cell-cell adhesion by classical cadherins: critical role for low-affinity dimerization through β–strand swapping. Proc. Natl Acad. Sci. USA 102, 8531–8536 (2005).
- 7.
Nose, A., Tsuji, K. & Takeichi, M. Localization of specificity determining sites in cadherin cell adhesion molecules. Cell 61, 147–155 (1990).
- 8.
Pertz, O. et al. A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation. EMBO J. 18, 1738–1747 (1999).
- 9.
Yap, A. S., Brieher, W. M. & Gumbiner, B. M. Molecular and functional analysis of cadherin-based adherens junctions. Annu. Rev. Cell Dev. Biol. 13, 119–146 (1997).
- 10.
Ozawa, M., Baribault, H. & Kemler, R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 8, 1711–1717 (1989).
- 11.
Reynolds, A. B. et al. Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Mol. Cell. Biol. 14, 8333–8342 (1994).
- 12.
Drees, F., Pokutta, S., Yamada, S., Nelson, W. J. & Weis, W. I. α-catenin is a molecular switch that binds E-cadherin-β-catenin and regulates actin-filament assembly. Cell 123, 903–915 (2005).
- 13.
Hulsken, J., Birchmeier, W. & Behrens, J. E-cadherin and APC compete for the interaction with β-catenin and the cytoskeleton. J. Cell Biol. 127, 2061–2069 (1994).
- 14.
Rimm, D. L., Koslov, E. R., Kebriaei, P., Cianci, C. D. & Morrow, J. S. α 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. Proc. Natl Acad. Sci. USA 92, 8813–8817 (1995).
- 15.
Rubinfeld, B., Souza, B., Albert, I., Munemitsu, S. & Polakis, P. The APC protein and E-cadherin form similar but independent complexes with α-catenin, β-catenin, and plakoglobin. J. Biol. Chem. 270, 5549–5555 (1995).
- 16.
Yamada, S., Pokutta, S., Drees, F., Weis, W. I. & Nelson, W. J. Deconstructing the cadherin-catenin-actin complex. Cell 123, 889–901 (2005).
- 17.
Behrens, J. et al. Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382, 638–642 (1996).
- 18.
Molenaar, M. et al. XTcf-3 transcription factor mediates β-catenin-induced axis formation in Xenopus embryos. Cell 86, 391–399 (1996).
- 19.
van de Wetering, M. et al. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88, 789–799 (1997).
- 20.
D'Souza-Schorey, C. Disassembling adherens junctions: breaking up is hard to do. Trends Cell Biol. 15, 19–26 (2005).
- 21.
Bremnes, R. M. et al. High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J. Clin. Oncol. 20, 2417–2428 (2002).
- 22.
Rakha, E. A., Abd El Rehim, D., Pinder, S. E., Lewis, S. A. & Ellis, I. O. E-cadherin expression in invasive non-lobular carcinoma of the breast and its prognostic significance. Histopathology 46, 685–693 (2005).
- 23.
Syrigos, K. N. et al. E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded tissues: correlation with histopathological grade, tumour stage and survival. Int. J. Cancer 64, 367–370 (1995).
- 24.
Wijnhoven, B. P., Pignatelli, M., Dinjens, W. N. & Tilanus, H. W. Reduced p120ctn expression correlates with poor survival in patients with adenocarcinoma of the gastroesophageal junction. J. Surg. Oncol. 92, 116–123 (2005).
- 25.
Zheng, Z. et al. Downregulation and abnormal expression of E-cadherin and β-catenin in nasopharyngeal carcinoma: close association with advanced disease stage and lymph node metastasis. Hum. Pathol. 30, 458–466 (1999).
- 26.
Perl, A. K., Wilgenbus, P., Dahl, U., Semb, H. & Christofori, G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392, 190–193 (1998).
- 27.
Derksen, P. W. et al. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 10, 437–449 (2006).
- 28.
Davis, M. A. & Reynolds, A. B. Blocked acinar development, E-cadherin reduction, and intraepithelial neoplasia upon ablation of p120-catenin in the mouse salivary gland. Dev. Cell 10, 21–31 (2006).
- 29.
Perez-Moreno, M., Song, W., Pasolli, H. A., Williams, S. E. & Fuchs, E. Loss of p120 catenin and links to mitotic alterations, inflammation, and skin cancer. Proc. Natl Acad. Sci. USA 105, 15399–15404 (2008).
- 30.
Kobielak, A. & Fuchs, E. Links between α-catenin, NF-κB, and squamous cell carcinoma in skin. Proc. Natl Acad. Sci. USA 103, 2322–2327 (2006).
- 31.
Kobielak, A. & Fuchs, E. α-catenin: at the junction of intercellular adhesion and actin dynamics. Nature Rev. Mol. Cell Biol. 5, 614–625 (2004).
- 32.
Green, K. J. & Gaudry, C. A. Are desmosomes more than tethers for intermediate filaments? Nature Rev. Mol. Cell Biol. 1, 208–216 (2000).
- 33.
Thomason, H. A., Scothern, A., McHarg, S. & Garrod, D. R. Desmosomes: adhesive strength and signalling in health and disease. Biochem. J. 429, 419–433 (2010).
- 34.
Chitaev, N. A. & Troyansovsky, S. M. Direct Ca2+-dependent heterophilic interaction between desmosomal cadherins, desmoglein and desmocollin, contributes to cell-cell adhesion. J. Cell Biol. 138, 193–201 (1997).
- 35.
Heupel, W. M., Zillikens, D., Drenckhahn, D. & Waschke, J. Pemphigus vulgaris IgG directly inhibit desmoglein3-mediated transinteraction. J. Immunol. 181, 1825–1834 (2008).
- 36.
Syed, S. E. et al. Molecular interactions between desmosomal cadherins. Biochem. J. 362, 317–327 (2002).
- 37.
Waschke, J., Bruggeman, P., Baumgartner, W., Zillkens, D. & Drenckhahn, D. Pemphigus foliaceus IgG causes dissociation of desmoglein 1-containing junctions without blocking desmoglein 1 transinteraction. J. Clin. Invest. 115, 3157–3165 (2005).
- 38.
Koeser, J., Troyanovsky, S. M., Grund, C. & Franke, W. W. De novo formation of desmosomes in cultured cells upon transfection of genes encoding specific desmosomal components. Exp. Cell Res. 285, 114–130 (2003).
- 39.
Nie, Z., Merritt, A., Rouhi-Parkouhi, M., Tabernero, L. & Garrod, D. Membrane-impermeable cross-linking provides evidence for homophilic, isoform-specific binding of desmosomal cadherins in epithelial cells. J. Biol. Chem. 286, 2143–2154 (2011).
- 40.
Runswick, S. K., O'Hare, M. J., Jones, L., Streuli, C. H. & Garrod, D. R. Desmosomal adhesion regulates epithelial morphogenesis and cell positioning. Nature Cell Biol. 3, 823–830 (2001).
- 41.
Witcher, L. L. et al. Desmosomal cadherin binding domains of plakoglobin. J. Biol. Chem. 271, 10904–10909 (1996).
- 42.
Mathur, M., Goodwin, L. & Cowin, P. Interactions of the cytoplasmic domain of the desmosomal cadherin Dsg1 with plakoglobin. J. Biol. Chem., 269, 14075–14080 (1994).
- 43.
Roh, J. Y. & Stanley, J. R. Plakoglobin binding by human Dsg3 (pemphigus vulgaris antigen) in keratinocytes requires the cadherin-like intracytoplasmic segment. J. Invest. Dermatol. 104, 720–724 (1995).
- 44.
Troyanovsky, S. M. et al. Identification of the plakoglobin-binding domain in desmoglein and its role in plaque assembly and intermediate filament anchorage. J. Cell Biol. 127, 151–160 (1994).
- 45.
Bonne, S. et al. Defining desmosomal plakophilin-3 interactions. J. Cell Biol. 161, 403–416 (2003).
- 46.
Chen, X., Bonne, S., Hatzfeld, M., van Roy, F. & Green, K. J. Protein binding and functional characterization of plakophilin 2. Evidence for its diverse roles in desmosomes and β-catenin signaling. J. Biol. Chem. 277, 10512–10522 (2002).
- 47.
Hatzfeld, M., Haffner, C., Schulze, K. & Vinzens, U. The function of plakophilin 1 in desmosome assembly and actin filament organization. J. Cell Biol. 149, 209–222 (2000).
- 48.
Butz, S., Stappert, J., Weissig, H. & Kemler, R. Plakoglobin and b-catenin: distinct but closely related. Science 257, 1142–1144 (1992).
- 49.
McCrea, P. D., Turck, C. W. & Gumbiner, B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science 254, 1359–1361 (1991).
- 50.
Nathke, I. S., Hinck, L., Swedlow, J. R., Papkoff, J. & Nelson, W. J. Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells. J. Cell Biol. 125, 1341–1352 (1994).
- 51.
Zhurinsky, J., Shtutman, M. & Ben-Ze'ev, A. Plakoglobin and β-catenin: protein interaction, regulation and biological roles. J. Cell Sci. 113, 3127–3139 (2000).
- 52.
Conacci-Sorrell, M. E. et al. Nr-CAM is a target gene of the β-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev. 16, 2058–2072 (2002).
- 53.
Mertens, C., Kuhn, C. & Franke, W. W. Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomsal plaque. J. Cell Biol. 135, 1009–1025 (1996).
- 54.
Bornslaeger, E. A. et al. Plakophilin 1 interferes with plakoglobin binding to desmoplakin, yet together with plakoglobin promotes clustering of desmosomal plaque complexes at cell-cell borders. J. Cell Sci. 114, 727–738 (2001).
- 55.
Kowalczyk, A. P. et al. The amino-terminal domain of desmoplakin binds to plakoglobin and clusters desmosomal cadherin-plakoglobin complexes. J. Cell Biol. 139, 773–784 (1997).
- 56.
Kouklis, P. D., Hutton, E. & Fuchs, E. Making a connection: direct binding between keratin intermediate filaments and desmosomal proteins. J. Cell Biol. 127, 1049–1060 (1994).
- 57.
Smith, E. A. & Fuchs, E. Defining the interactions between intermediate filaments and desmosomes. J. Cell Biol. 141, 1229–1241 (1998).
- 58.
Ihrie, R. A. et al. Perp is a p63-regulated gene essential for epithelial integrity. Cell 120, 843–856 (2005).
- 59.
Attardi, L. D. et al. PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes Dev. 14, 704–718 (2000).
- 60.
Carroll, D. K., Brugge, J. S. & Attardi, L. D. p63, cell adhesion, and survival. Cell Cycle 6, 255–261 (2007).
- 61.
Flores, E. R. et al. Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cell 7, 363–373 (2005).
- 62.
Den, Z., Cheng, X., Merched-Sauvage, M. & Koch, P. J. Desmocollin 3 is required for pre-implantation development of the mouse embryo. J. Cell Sci. 199, 482–489 (2006).
- 63.
Eshkind, L. et al. Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells. Eur. J. Cell Biol. 81, 592–598 (2002).
- 64.
Gallicano, G. I. et al. Desmoplakin is required early in development for assembly of desmosomes and cytoskeletal linkage. J. Cell Biol. 143, 2009–2022 (1998).
- 65.
Bierkamp, C., Mclaughlin, K. J., Schwarz, H., Huber, O. & Kemler, R. Embryonic heart and skin defects in mice lacking plakglobin. Dev. Biol. 180, 780–785 (1996).
- 66.
Ruiz, P. et al. Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart. J. Cell Biol. 135, 215–225 (1996).
- 67.
Koch, P. J. et al. Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris. J. Cell Biol. 137, 1091–1102 (1997).
- 68.
Vasioukhin, V., Bowers, E., Bauer, C., Degenstein, L. & Fuchs, E. Desmoplakin is essential in epidermal sheet formation. Nature Cell Biol. 3, 1076–1085 (2001).
- 69.
Chidgey, M. et al. Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation. J. Cell Biol. 155, 821–832 (2001).
- 70.
Chen, J., Den, Z. & Koch, P. J. Loss of desmocollin 3 in mice leads to epidermal blistering. J. Cell Sci. 121, 2844–2849 (2008).
- 71.
Chidgey, M. Desmosomes and disease: an update. Histol. Histopathol. 17, 1179–1192 (2002).
- 72.
Brennan, D. & Mahoney, M. G. Increased expression of Dsg2 in malignant skin carcinomas: a tissue-microarrary based study. Cell Adh. Migr. 3, 148–154 (2009).
- 73.
Chen, Y. J. et al. DSG3 is overexpressed in head neck cancer and is a potential moelcular target for inhibition of oncogenesis. Oncogene 26, 467–476 (2007).
- 74.
Furukawa, C. et al. Plakophilin 3 oncogene as prognostic marker and therapeutic target for lung cancer. Cancer Res. 65, 7102–7110 (2005).
- 75.
Kurzen, H., Munzing, I. & Hartschuh, W. Expression of desmosomal proteins in squamous cell carcinomas of the skin. J. Cutan. Pathol. 30, 621–630 (2003).
- 76.
Breuninger, S. et al. Desmosomal plakophilins in the prostate and prostatic adenocarcinomas: implications for diagnosis and tumor progression. Am. J. Pathol. 176, 2509–2519 (2010).
- 77.
Alazawi, W. O., Morris, L. S., Stanley, M. A., Garrod, D. R. & Coleman, N. Altered expression of desmosomal components in high-grade squamous intraepithelial lesions of the cervix. Virchows Arch. 443, 51–56 (2003).
- 78.
Alroy, J., Pauli, B. U. & Weinstein, R. S. Correlation between numbers of desmosomes and the aggressiveness of transitional cell carcinoma in human urinary bladder. Cancer 47, 104–112 (1981).
- 79.
de Boer, C. J. et al. Changing roles of cadherins and catenins during progression of squamous intraepithelial lesions in the uterine cervix. Am. J. Pathol. 155, 505–515 (1999).
- 80.
Demirag, G. G., Sullu, Y., Gurgenyatagi, D., Okumus, N. O. & Yucel, I. Expression of plakophilins (PKP1, PKP2, and PKP3) in gastric cancers. Diagn. Pathol. 6, 1 (2011).
- 81.
Harada, T., Shinohara, M., Nakamura, S., Shimada, M. & Oka, M. Immunohistochemical detection of desmosomes in oral squamous cell carcinomas: correlation with differentiation, mode of invasion, and metastatic potential. Int. J. Oral Maxillofac. Surg. 21, 346–349 (1992).
- 82.
Hiraki, A. et al. Immunohistochemical staining of desmosomal components in oral squamous cell carcinomas and its association with tumour behaviour. Br. J. Cancer 73, 1491–1497 (1996).
- 83.
Kocher, O., Amaudruz, M., Schindler, A. M. & Gabbiani, G. Desmosomes and gap junctions in precarcinomatous and carcinomatous conditions of squamous epithelia. An electron microscopic and morphometrical study. J. Submicrosc. Cytol. 13, 267–281 (1981).
- 84.
Nei, H. et al. Expression of component desmosomal proteins in uterine endometrial carcinoma and their relation to cellular differentiation. Cancer 78, 461–470 (1996).
- 85.
Tada, H., Hatoko, M., Tanaka, A., Kuwahara, M. & Muramatsu, T. Expression of desmoglein I and plakoglobin in skin carcinomas. J. Cutan. Pathol. 27, 24–29 (2000).
- 86.
Biedermann, K. et al. Desmoglein 2 is expressed abnormally rather than mutated in familial and sporadic gastric cancer. J. Pathol. 207, 199–206 (2005).
- 87.
Depondt, J., Shabana, A. H., Florescu-Zorila, S., Gehanno, P. & Forest, N. Down-regulation of desmosomal molecules in oral and pharyngeal squamous cell carcinomas as a marker for tumour growth and distant metastasis. Eur. J. Oral Sci. 107, 183–193 (1999).
- 88.
Kahn, K. et al. Desmocollin switching in colorectal cancer. Br. J. Cancer 95, 1367–1370 (2006).
- 89.
Oshiro, M. M. et al. Epigenetic silencing of DSC3 is a common event in human breast cancer. Breast Cancer Res. 7, R669–R680 (2005).
- 90.
Papagerakis, S. et al. Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. Hum. Pathol. 40, 1320–1329 (2009).
- 91.
Shiina, H. et al. Functional loss of the γ-catenin gene through epigenetic and genetic pathways in human prostate cancer. Cancer Res. 65, 2130–2138 (2005).
- 92.
Sobolik-Delmaire, T., Katafiasz, D., Keim, S. A., Mahoney, M. G. & Wahl, J. K. Decreased plakophilin-1 expression promotes increased motility in head and neck squamous cell carcinoma cells. Cell Commun. Adhes. 14, 99–109 (2007).
- 93.
Winn, R. A. et al. γ-catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth. Oncogene 21, 7497–7506 (2002).
- 94.
Yashiro, M., Nishioka, N. & Hirakawa, K. Decreased expression of the adhesion molecule desmoglein-2 is associated with diffuse-type gastric carcinoma. Eur. J. Cancer 42, 2397–2403 (2006).
- 95.
Wong, M. P. et al. Loss of desmoglein1 expression associated with worse prognosis in head and neck squamous cell carcinoma patients. Pathology 40, 611–616 (2008).
- 96.
Collins, J. E., Taylor, I. & Garrod, D. R. A study of desmosomes in colorectal carcinoma. Br. J. Cancer 62, 796–805 (1990).
- 97.
Hakimelahi, S. et al. Plakoglobin regulates the expression of the anti-apoptotic protein BCL-2. J. Biol. Chem. 275, 10905–10911 (2000).
- 98.
Kolligs, F. T. et al. γ-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of β-catenin. Genes Dev. 14, 1319–1331 (2000).
- 99.
Brennan, D. et al. Suprabasal Dsg2 expression in transgenic mouse skin congers a hyperproliferative and apoptosis-resistant phenotype to keratinocytes. J. Cell Sci. 120, 758–771 (2007).
- 100.
Tselepis, C., Chidgey, M., North, A. & Garrod, D. Desmosomal adhesion inhibits invasive behavior. Proc. Natl Acad. Sci. USA 95, 8064–8069 (1998).
- 101.
Simcha, I., Geiger, B., Yehuda-Levenberg, S., Salomon, D. & Ben-Ze'ev, A. Suppression of tumorigenicity by plakoglobin: an augmenting effect of N-cadherin. J. Cell Biol. 133, 199–209 (1996).
- 102.
Reiger-Christ, K. M. et al. Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses cell migration and tumorigenic potential. Br. J. Cancer 92, 2153–2159 (2005).
- 103.
De Bruin, A. et al. Loss of invasiveness in squamous cell carcinoma cells overexpressing desmosomal cadherins. Cell Adhes. Commun. 7, 13–28 (1999).
- 104.
Kundu, S. T. et al. Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis. Int. J. Cancer 123, 2303–2314 (2008).
- 105.
Caca, K. et al. β- and γ-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. Cell Growth Differ. 10, 369–376 (1999).
- 106.
Chun, M. G. & Hanahan, D. Genetic deletion of the desmosomal component desmoplakin promotes tumor microinvasion in a mouse model of pancreatic neuroendocrine carcinogenesis. PLoS Genet. 6, e1001120 (2010).
- 107.
Lewis, J. E., Jensen, P. J. & Wheelock, M. J. Cadherin function is required for human keratinocytes to assemble desmosomes and stratify in response to calcium. J. Invest. Dermatol. 102, 870–877 (1994).
- 108.
Beaudry, V. G. et al. Loss of the p53/p63 regulated desmosomal protein Perp promotes tumorigenesis. PLoS Genet. 6, e1001168 (2010).
- 109.
Melnikova, V. O. & Ananthaswamy, H. N. Cellular and molecular events leading to the development of skin cancer. Mutat. Res. 571, 91–106 (2005).
- 110.
Karnovsky, A. & Klymkowsky, M. W. Anterior axis duplication in Xenopus induced by the over-expression of the cadherin-binding protein plakoglobin. Proc. Natl Acad. Sci. USA 92, 4522–4526 (1995).
- 111.
Klymkowsky, M. W., Williams, B. O., Barish, G. D., Varmus, H. E. & Vourgourakis, Y. E. Membrane-anchored plakoglobins have multiple mechanisms of action in Wnt signaling. Mol. Biol. Cell 10, 3151–3169 (1999).
- 112.
Merriam, J. M., Rubenstein, A. B. & Klymkowsky, M. W. Cytoplasmically anchored plakoglobin induces a WNT-like phenotype in Xenopus. Dev. Biol. 185, 67–81 (1997).
- 113.
Miller, J. R. & Moon, R. T. Analysis of the signaling activities of localization mutants of β-catenin during axis specification in Xenopus. J. Cell Biol. 139, 229–243 (1997).
- 114.
Simcha, I. et al. Differential nuclear translocation and transactivation potential of β-catenin and plakoglobin. J. Cell Biol. 141, 1433–1448 (1998).
- 115.
Li, L., Chapman, K., Hu, X., Wong, A. & Pasdar, M. Modulation of the oncogenic potential of β-catenin by the subcellular distribution of plakoglobin. Mol. Carcinog. 46, 824–838 (2007).
- 116.
Salomon, D. et al. Regulation of β-catenin levels and localization by overexpression of plakoglobin and inhibition of the ubiquitin-proteasome system. J. Cell Biol. 139, 1325–1335 (1997).
- 117.
Miravet, S. et al. Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates β-catenin-mediated transcription. Mol. Cell. Biol. 23, 7391–7402 (2003).
- 118.
Zhurinsky, J., Shtutman, M. & Ben-Ze'ev, A. Differential mechanisms of LEF/TCF family-dependent transcriptional activation by β-catenin and plakoglobin. Mol. Cell. Biol. 20, 4238–4252 (2000).
- 119.
Shtutman, M. et al. The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway. Proc. Natl Acad. Sci. USA 96, 5522–5527 (1999).
- 120.
Williamson, L. et al. Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin. EMBO J. 25, 3298–3309 (2006).
- 121.
Maeda, O. et al. Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line. Oncogene 23, 964–972 (2004).
- 122.
Teuliere, J. et al. β-catenin-dependent and -independent effects of DeltaN-plakoglobin on epidermal growth and differentiation. Mol. Cell. Biol. 24, 8649–8661 (2004).
- 123.
Garcia-Gras, E. et al. Suppression of canonical Wnt/β-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy. J. Clin. Invest. 116, 2012–2021 (2006).
- 124.
Li, J. et al. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of β-catenin signaling. Mol. Cell. Biol. 31, 1134–1144 (2011).
- 125.
Martin, E. D., Moriarty, M. A., Byrnes, L. & Grealy, M. Plakoglobin has both structural and signalling roles in zebrafish development. Dev. Biol. 327, 83–96 (2009).
- 126.
Schmidt, A. et al. Plakophilins 1a and 1b: widespread nuclear proteins recruited in specific epithelial cells as desmosomal plaque components. Cell Tissue Res. 290, 481–499 (1997).
- 127.
Sobolik-Delmaire, T., Reddy, R., Pashaj, A., Roberts, B. J. & Wahl, J. K. Plakophilin-1 localizes to the nucleus and interacts with single-stranded DNA. J. Invest. Dermatol. 130, 2638–2646 (2010).
- 128.
Wolf, A. et al. Plakophilin 1 stimulates translation by promoting eIF4A1 activity. J. Cell Biol. 188, 463–471 (2010).
- 129.
Hofmann, I. et al. Identification of the junctional plaque protein plakophilin 3 in cytoplasmic particles containing RNA-binding proteins and the recruitment of plakophilins 1 and 3 to stress granules. Mol. Biol. Cell 17, 1388–1398 (2006).
- 130.
Papagerakis, S., Shabana, A. H., Depondt, J., Gehanno, P. & Forest, N. Immunohistochemical localization of plakophilins (PKP1, PKP2, PKP3, and p0071) in primary oropharyngeal tumors: correlation with clinical parameters. Hum. Pathol. 34, 565–572 (2003).
- 131.
Berkowitz, P. et al. Desmosome signaling. Inhibition of p38MAPK prevents pemphigus vulgaris IgG-induced cytoskeleton reorganization. J. Biol. Chem. 280, 23778–23784 (2005).
- 132.
Wan, H., South, A. P. & Hart, I. R. Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference. Exp. Cell Res. 313, 2336–2344 (2007).
- 133.
Garrod, D. R., Berika, M. Y., Bardsley, W. F., Holmes, D. & Tabernero, L. Hyper-adhesion in desmosomes: its regulation in wound healing and possible relationship to cadherin crystal structure. J. Cell Sci. 118, 5743–5754 (2005).
- 134.
Kimura, T. E., Merritt, A. J. & Garrod, D. R. Calcium-independent desmosomes of keratinocytes are hyper-adhesive. J. Invest. Dermatol. 127, 775–781 (2007).
- 135.
Luthra, R. et al. Gene expression profiling of localized esophageal carcinomas: association with pathologic response to preoperative chemoradiation. J. Clin. Oncol. 24, 259–267 (2006).
Acknowledgements
R.L.D. is supported by the American Cancer Society New England-SpinOdyssey Postdoctoral Fellowship. L.D.A. is supported by the US National Cancer Institute (NCI) (R01 CA093665). The authors would like to thank K. Bieging, D. Jiang and S. Baron for thoughtful comments on the manuscript. The authors apologize to those authors whose work could not be cited owing to space limitations.
Author information
Affiliations
Rachel L. Dusek and Laura D. Attardi are at The Departments of Radiation Oncology and Genetics, Stanford University School of Medicine, Room 1255, 269 Campus Drive, Stanford, California 94305, USA.
- Rachel L. Dusek
- & Laura D. Attardi
Authors
Search for Rachel L. Dusek in:
Search for Laura D. Attardi in:
Competing interests
The authors declare no competing financial interests.
Corresponding author
Correspondence to Laura D. Attardi.
Rights and permissions
To obtain permission to re-use content from this article visit RightsLink.
About this article
Further reading
-
SOX30 is a key regulator of desmosomal gene suppressing tumor growth and metastasis in lung adenocarcinoma
Journal of Experimental & Clinical Cancer Research (2018)
-
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancer
Cell Death & Disease (2018)
-
Differential Proteome Analysis of Human Neuroblastoma Xenograft Primary Tumors and Matched Spontaneous Distant Metastases
Scientific Reports (2018)
-
Role of protein kinase N2 (PKN2) in cigarette smoke-mediated oncogenic transformation of oral cells
Journal of Cell Communication and Signaling (2018)
-
Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2
Journal of Cancer Research and Clinical Oncology (2017)
