The Journal of Cell Biology, Vol 128, 949-957, Copyright © 1995 by The Rockefeller University Press

ARTICLES

Association of p120, a tyrosine kinase substrate, with E- cadherin/catenin complexes

S Shibamoto, M Hayakawa, K Takeuchi, T Hori, K Miyazawa, N Kitamura, KR Johnson, MJ Wheelock, N Matsuyoshi and M Takeichi
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.

p120 was originally identified as a substrate of pp60src and several receptor tyrosine kinases, but its function is not known. Recent studies revealed that this protein shows homology to a group of proteins, beta-catenin/Armadillo and plakoglobin (gamma-catenin), which are associated with the cell adhesion molecules cadherins. In this study, we examined whether p120 is associated with E-cadherin using the human carcinoma cell line HT29, as well as other cell lines, which express both of these proteins. When proteins that copurified with E- cadherin were analyzed, not only alpha-catenin, beta-catenin, and plakoglobin but also p120 were detected. Conversely, immunoprecipitates of p120 contained E-cadherin and all the catenins, although a large subpopulation of p120 was not associated with E-cadherin. Analysis of these immunoprecipitates suggests that 20% or less of the extractable E- cadherin is associated with p120. When p120 immunoprecipitation was performed with cell lysates depleted of E-cadherin, beta-catenin was no longer coprecipitated, and the amount of plakoglobin copurified was greatly reduced. This finding suggests that there are various forms of p120 complexes, including p120/E-cadherin/beta-catenin and p120/E- cadherin/plakoglobin complexes; this association profile contrasts with the mutually exclusive association of beta-catenin and plakoglobin with cadherins. When the COOH-terminal catenin binding site was truncated from E-cadherin, not only beta-catenin but also p120 did not coprecipitate with this mutated E-cadherin. Immunocytological studies showed that p120 colocalized with E-cadherin at cell-cell contact sites, even after non-ionic detergent extraction. Treatment of cells with hepatocyte growth factor/scatter factor altered the level of tyrosine phosphorylation of p120 as well as of beta-catenin and plakoglobin. These results suggest that p120 associates with E-cadherin at its COOH-terminal region, but the mechanism for this association differs from that for the association of beta-catenin and plakoglobin with E-cadherin, and thus, that p120, whose function could be modulated by growth factors, may play a unique role in regulation of the cadherin- catenin adhesion system.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Franke, W. W. (2009). Discovering the Molecular Components of Intercellular Junctions--A Historical View. Cold Spring Harb. Perspect. Biol. 1: a003061-a003061 [Abstract] [Full Text]  
• Fukasawa, H., Bornheimer, S., Kudlicka, K., Farquhar, M. G. (2009). Slit Diaphragms Contain Tight Junction Proteins. J. Am. Soc. Nephrol. 20: 1491-1503 [Abstract] [Full Text]  
• Ogden, S. R., Wroblewski, L. E., Weydig, C., Romero-Gallo, J., O'Brien, D. P., Israel, D. A., Krishna, U. S., Fingleton, B., Reynolds, A. B., Wessler, S., Peek, R. M. Jr (2008). p120 and Kaiso Regulate Helicobacter pylori-induced Expression of Matrix Metalloproteinase-7. Mol. Biol. Cell 19: 4110-4121 [Abstract] [Full Text]  
• Xie, Z., Bikle, D. D. (2007). The Recruitment of Phosphatidylinositol 3-Kinase to the E-cadherin-Catenin Complex at the Plasma Membrane Is Required for Calcium-induced Phospholipase C-{gamma}1 Activation and Human Keratinocyte Differentiation. J. Biol. Chem. 282: 8695-8703 [Abstract] [Full Text]  
• Gurlek, A., Karavitaki, N., Ansorge, O., Wass, J. A H (2007). What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. Eur J Endocrinol 156: 143-153 [Abstract] [Full Text]  
• Segawa, Y., Suga, H., Iwabe, N., Oneyama, C., Akagi, T., Miyata, T., Okada, M. (2006). Functional development of Src tyrosine kinases during evolution from a unicellular ancestor to multicellular animals. Proc. Natl. Acad. Sci. USA 103: 12021-12026 [Abstract] [Full Text]  
• Shibata, T., Kokubu, A., Sekine, S., Kanai, Y., Hirohashi, S. (2004). Cytoplasmic p120ctn Regulates the Invasive Phenotypes of E-Cadherin-Deficient Breast Cancer. Am. J. Pathol. 164: 2269-2278 [Abstract] [Full Text]  
• Franz, C. M., Ridley, A. J. (2004). p120 Catenin Associates with Microtubules: INVERSE RELATIONSHIP BETWEEN MICROTUBULE BINDING AND RHO GTPase REGULATION. J. Biol. Chem. 279: 6588-6594 [Abstract] [Full Text]  
• Davis, M. A., Ireton, R. C., Reynolds, A. B. (2003). A core function for p120-catenin in cadherin turnover. JCB 163: 525-534 [Abstract] [Full Text]  
• Roczniak-Ferguson, A., Reynolds, A. B. (2003). Regulation of p120-catenin nucleocytoplasmic shuttling activity. J. Cell Sci. 116: 4201-4212 [Abstract] [Full Text]  
• Rajasekaran, A. K., Rajasekaran, S. A. (2003). Role of Na-K-ATPase in the assembly of tight junctions. Am. J. Physiol. Renal Physiol. 285: F388-F396 [Abstract] [Full Text]  
• Wahl, J. K. III, Kim, Y. J., Cullen, J. M., Johnson, K. R., Wheelock, M. J. (2003). N-cadherin-Catenin Complexes Form Prior to Cleavage of the Proregion and Transport to the Plasma Membrane. J. Biol. Chem. 278: 17269-17276 [Abstract] [Full Text]  
• Hatzfeld, M., Green, K. J., Sauter, H. (2003). Targeting of p0071 to desmosomes and adherens junctions is mediated by different protein domains. J. Cell Sci. 116: 1219-1233 [Abstract] [Full Text]  
• Lee, N. P.Y., Mruk, D., Lee, W. M., Cheng, C. Y. (2003). Is the Cadherin/Catenin Complex a Functional Unit of Cell-Cell Actin-Based Adherens Junctions in the Rat Testis?. Biol. Reprod. 68: 489-508 [Abstract] [Full Text]  
• Kawano, R., Matsuo, N., Tanaka, H., Nasu, M., Yoshioka, H., Shirabe, K. (2002). Identification and Characterization of a Soluble Cadherin-7 Isoform Produced by Alternative Splicing. J. Biol. Chem. 277: 47679-47685 [Abstract] [Full Text]  
• Ireton, R. C., Davis, M. A., van Hengel, J., Mariner, D. J., Barnes, K., Thoreson, M. A., Anastasiadis, P. Z., Matrisian, L., Bundy, L. M., Sealy, L., Gilbert, B., van Roy, F., Reynolds, A. B. (2002). A novel role for p120 catenin in E-cadherin function. JCB 159: 465-476 [Abstract] [Full Text]  
• Gopalakrishnan, S., Dunn, K. W., Marrs, J. A. (2002). Rac1, but not RhoA, signaling protects epithelial adherens junction assembly during ATP depletion. Am. J. Physiol. Cell Physiol. 283: C261-C272 [Abstract] [Full Text]  
• Dahl, U., Sjodin, A., Larue, L., Radice, G. L., Cajander, S., Takeichi, M., Kemler, R., Semb, H. (2002). Genetic Dissection of Cadherin Function during Nephrogenesis. Mol. Cell. Biol. 22: 1474-1487 [Abstract] [Full Text]  
• Aho, S., Levansuo, L., Montonen, O., Kari, C., Rodeck, U., Uitto, J. (2002). Specific sequences in p120ctn determine subcellular distribution of its multiple isoforms involved in cellular adhesion of normal and malignant epithelial cells. J. Cell Sci. 115: 1391-1402 [Abstract] [Full Text]  
• Montonen, O., Aho, M., Uitto, J., Aho, S. (2001). Tissue Distribution and Cell Type-specific Expression of p120ctn Isoforms. J. Histochem. Cytochem. 49: 1487-1496 [Abstract] [Full Text]  
• Omelchenko, T., Fetisova, E., Ivanova, O., Bonder, E. M., Feder, H., Vasiliev, J. M., Gelfand, I. M. (2001). Contact interactions between epitheliocytes and fibroblasts: Formation of heterotypic cadherin-containing adhesion sites is accompanied by local cytoskeletal reorganization. Proc. Natl. Acad. Sci. USA 10.1073/pnas.151247698v1 [Abstract] [Full Text]  
• Decaens, C., Cassio, D. (2001). Spatiotemporal expression of catenins, ZO-1, and occludin during early polarization of hepatic WIF-B9 cells. Am. J. Physiol. Cell Physiol. 280: C527-C539 [Abstract] [Full Text]  
• Rajasekaran, S. A., Palmer, L. G., Quan, K., Harper, J. F., Ball, W. J. Jr., Bander, N. H., Soler, A. P., Rajasekaran, A. K. (2001). Na,K-ATPase {beta}-Subunit Is Required for Epithelial Polarization, Suppression of Invasion, and Cell Motility. Mol. Biol. Cell 12: 279-295 [Abstract] [Full Text]  
• Ozawa, M, Ohkubo, T (2001). Tyrosine phosphorylation of p120(ctn) in v-Src transfected L cells depends on its association with E-cadherin and reduces adhesion activity. J. Cell Sci. 114: 503-512 [Abstract]  
• Grosheva, I, Shtutman, M, Elbaum, M, Bershadsky, A. (2001). p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion. J. Cell Sci. 114: 695-707 [Abstract]  
• Kim, J.-B., Islam, S., Kim, Y. J., Prudoff, R. S., Sass, K. M., Wheelock, M. J., Johnson, K. R. (2000). N-Cadherin Extracellular Repeat 4 Mediates Epithelial to Mesenchymal Transition and Increased Motility. JCB 151: 1193-1206 [Abstract] [Full Text]  
• Bush, K. T., Tsukamoto, T., Nigam, S. K. (2000). Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial ischemia. Am. J. Physiol. Renal Physiol. 278: F847-F852 [Abstract] [Full Text]  
• Zondag, G. C. M., Reynolds, A. B., Moolenaar, W. H. (2000). Receptor Protein-tyrosine Phosphatase RPTP{micro} Binds to and Dephosphorylates the Catenin p120ctn. J. Biol. Chem. 275: 11264-11269 [Abstract] [Full Text]  
• Hatzfeld, M., Haffner, C., Schulze, K., Vinzens, U. (2000). The Function of Plakophilin 1 in Desmosome Assembly and Actin Filament Organization. JCB 149: 209-222 [Abstract] [Full Text]  
• Leser, J., Beil, M. F., Musa, O. A., Adler, G., Lutz, M. P. (2000). Regulation of adherens junction protein p120ctn by 10 nM CCK precedes actin breakdown in rat pancreatic acini. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G486-G491 [Abstract] [Full Text]  
• Shan, W.-S., Tanaka, H., Phillips, G. R., Arndt, K., Yoshida, M., Colman, D. R., Shapiro, L. (2000). Functional Cis-Heterodimers of N- and R-Cadherins. JCB 148: 579-590 [Abstract] [Full Text]  
• Thoreson, M. A., Anastasiadis, P. Z., Daniel, J. M., Ireton, R. C., Wheelock, M. J., Johnson, K. R., Hummingbird, D. K., Reynolds, A. B. (2000). Selective Uncoupling of P120ctn from E-Cadherin Disrupts Strong Adhesion. JCB 148: 189-202 [Abstract] [Full Text]  
• Anastasiadis, P., Reynolds, A. (2000). The p120 catenin family: complex roles in adhesion, signaling and cancer. J. Cell Sci. 113: 1319-1334 [Abstract]  
• Hiiragi, T., Sasaki, H., Nagafuchi, A., Sabe, H., Shen, S. C., Matsuki, M., Yamanishi, K., Tsukita, S. (1999). Transglutaminase Type 1 and Its Cross-linking Activity Are Concentrated at Adherens Junctions in Simple Epithelial Cells. J. Biol. Chem. 274: 34148-34154 [Abstract] [Full Text]  
• Nieman, M. T., Prudoff, R. S., Johnson, K. R., Wheelock, M. J. (1999). N-Cadherin Promotes Motility in Human Breast Cancer Cells Regardless of Their E-Cadherin Expression. JCB 147: 631-644 [Abstract] [Full Text]  
• Ohkubo, T., Ozawa, M. (1999). p120ctn Binds to the Membrane-proximal Region of the E-cadherin Cytoplasmic Domain and Is Involved in Modulation of Adhesion Activity. J. Biol. Chem. 274: 21409-21415 [Abstract] [Full Text]  
• Aono, S., Nakagawa, S., Reynolds, A. B., Takeichi, M. (1999). p120ctn Acts as an Inhibitory Regulator of Cadherin Function in Colon Carcinoma Cells. JCB 145: 551-562 [Abstract] [Full Text]  
• Daniel, J. M., Reynolds, A. B. (1999). The Catenin p120ctn Interacts with Kaiso, a Novel BTB/POZ Domain Zinc Finger Transcription Factor. Mol. Cell. Biol. 19: 3614-3623 [Abstract] [Full Text]  
• Pötter, E., Bergwitz, C., Brabant, G. (1999). The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues. Endocr. Rev. 20: 207-239 [Abstract] [Full Text]  
• Wong, V., Ching, D., McCrea, P. D., Firestone, G. L. (1999). Glucocorticoid Down-regulation of Fascin Protein Expression Is Required for the Steroid-induced Formation of Tight Junctions and Cell-Cell Interactions in Rat Mammary Epithelial Tumor Cells. J. Biol. Chem. 274: 5443-5453 [Abstract] [Full Text]  
• Lu, Q., Paredes, M., Medina, M., Zhou, J., Cavallo, R., Peifer, M., Orecchio, L., Kosik, K. S. (1999). {delta}-catenin, an Adhesive Junction-associated Protein Which Promotes Cell Scattering. JCB 144: 519-532 [Abstract] [Full Text]  
• YEAMAN, C., GRINDSTAFF, K. K., NELSON, W. J. (1999). New Perspectives on Mechanisms Involved in Generating Epithelial Cell Polarity. Physiol. Rev. 79: 73-98 [Abstract] [Full Text]  
• Gulino, D., Delachanal, E., Concord, E., Genoux, Y., Morand, B., Valiron, M.-O., Sulpice, E., Scaife, R., Alemany, M., Vernet, T. (1998). Alteration of Endothelial Cell Monolayer Integrity Triggers Resynthesis of Vascular Endothelium Cadherin. J. Biol. Chem. 273: 29786-29793 [Abstract] [Full Text]  
• Ozawa, M., Kemler, R. (1998). The Membrane-proximal Region of the E-Cadherin Cytoplasmic Domain Prevents Dimerization and Negatively Regulates Adhesion Activity. JCB 142: 1605-1613 [Abstract] [Full Text]  
• Chitaev, N. A., Troyanovsky, S. M. (1998). Adhesive But Not Lateral E-cadherin Complexes Require Calcium and Catenins for Their Formation. JCB 142: 837-846 [Abstract] [Full Text]  
• Efstathiou, J. A., Pignatelli, M. (1998). Modulation of Epithelial Cell Adhesion in Gastrointestinal Homeostasis. Am. J. Pathol. 153: 341-347 [Full Text]  
• Calautti, E., Cabodi, S., Stein, P. L., Hatzfeld, M., Kedersha, N., Paolo Dotto, G. (1998). Tyrosine Phosphorylation and Src Family Kinases Control Keratinocyte Cell-Cell Adhesion. JCB 141: 1449-1465 [Abstract] [Full Text]  
• Yap, A. S., Niessen, C. M., Gumbiner, B. M. (1998). The Juxtamembrane Region of the Cadherin Cytoplasmic Tail Supports Lateral Clustering, Adhesive Strengthening, and Interaction with p120ctn. JCB 141: 779-789 [Abstract] [Full Text]  
• Efstathiou, J. A., Noda, M., Rowan, A., Dixon, C., Chinery, R., Jawhari, A., Hattori, T., Wright, N. A., Bodmer, W. F., Pignatelli, M. (1998). Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells. Proc. Natl. Acad. Sci. USA 95: 3122-3127 [Abstract] [Full Text]  
• Ozawa, M., Kemler, R. (1998). Altered Cell Adhesion Activity by Pervanadate Due to the Dissociation of alpha -Catenin from the E-Cadherin·Catenin Complex. J. Biol. Chem. 273: 6166-6170 [Abstract] [Full Text]  
• Sako, Y., Nagafuchi, A., Tsukita, S., Takeichi, M., Kusumi, A. (1998). Cytoplasmic Regulation of the Movement of E-Cadherin on the Free Cell Surface as Studied by Optical Tweezers and Single Particle Tracking: Corralling and Tethering by the Membrane Skeleton. JCB 140: 1227-1240 [Abstract] [Full Text]  
• Herrera, R (1998). Modulation of hepatocyte growth factor-induced scattering of HT29 colon carcinoma cells. Involvement of the MAPK pathway. J. Cell Sci. 111: 1039-1049 [Abstract]  
• Ratcliffe, M. J., Rubin, L. L., Staddon, J. M. (1997). Dephosphorylation of the Cadherin-associated p100/p120 Proteins in Response to Activation of Protein Kinase C in Epithelial Cells. J. Biol. Chem. 272: 31894-31901 [Abstract] [Full Text]  
• Takaishi, K., Sasaki, T., Kotani, H., Nishioka, H., Takai, Y. (1997). Regulation of Cell-Cell Adhesion by Rac and Rho Small G Proteins in MDCK Cells. JCB 139: 1047-1059 [Abstract] [Full Text]  
• Yanagawa, S.-i., Lee, J.-S., Haruna, T., Oda, H., Uemura, T., Takeichi, M., Ishimoto, A. (1997). Accumulation of Armadillo Induced by Wingless, Dishevelled, and Dominant-negative Zeste-white 3 Leads to Elevated DE-cadherin in Drosophila Clone 8 Wing Disc Cells. J. Biol. Chem. 272: 25243-25251 [Abstract] [Full Text]  
• Garver, T. D., Ren, Q., Tuvia, S., Bennett, V. (1997). Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin. JCB 137: 703-714 [Abstract] [Full Text]  
• Finnemann, S., Mitrik, I., Hess, M., Otto, G., Wedlich, D. (1997). Uncoupling of XB/U-Cadherin-Catenin Complex Formation from Its Function in Cell-Cell Adhesion. J. Biol. Chem. 272: 11856-11862 [Abstract] [Full Text]  
• Kreft, B., Berndorff, D., Bottinger, A., Finnemann, S., Wedlich, D., Hortsch, M., Tauber, R., Gessner, R. (1997). LI-Cadherin-mediated Cell-Cell Adhesion Does Not Require Cytoplasmic Interactions. JCB 136: 1109-1121 [Abstract] [Full Text]  
• Shibata, T., Shimoyama, Y., Gotoh, M., Hirohashi, S. (1997). Identification of Human Cadherin-14, a Novel Neurally Specific Type II Cadherin, by Protein Interaction Cloning. J. Biol. Chem. 272: 5236-5240 [Abstract] [Full Text]  
• Papkoff, J., Papkoff, J. (1997). Regulation of Complexed and Free Catenin Pools by Distinct Mechanisms. DIFFERENTIAL EFFECTS OF Wnt-1 AND v-Src. J. Biol. Chem. 272: 4536-4543 [Abstract] [Full Text]  
• Lampugnani, M., Corada, M, Andriopoulou, P, Esser, S, Risau, W, Dejana, E (1997). Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells. J. Cell Sci. 110: 2065-2077 [Abstract]  
• Hirase, T, Staddon, J., Saitou, M, Ando-Akatsuka, Y, Itoh, M, Furuse, M, Fujimoto, K, Tsukita, S, Rubin, L. (1997). Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci. 110: 1603-1613 [Abstract]  
• Ayalon, O, Geiger, B (1997). Cyclic changes in the organization of cell adhesions and the associated cytoskeleton, induced by stimulation of tyrosine phosphorylation in bovine aortic endothelial cells. J. Cell Sci. 110: 547-556 [Abstract]  
• Pai, L.-M., Kirkpatrick, C., Blanton, J., Oda, H., Takeichi, M., Peifer, M. (1996). Drosophila alpha -Catenin and E-cadherin Bind to Distinct Regions of Drosophila Armadillo. J. Biol. Chem. 271: 32411-32420 [Abstract] [Full Text]  
• Miller, J R, Moon, R T (1996). Signal transduction through beta-catenin and specification of cell fate during embryogenesis.. Genes Dev. 10: 2527-2539  
• Troyanovsky, R., Chitaev, N., Troyanovsky, S. (1996). Cadherin binding sites of plakoglobin: localization, specificity and role in targeting to adhering junctions. J. Cell Sci. 109: 3069-3078 [Abstract]  
• Hatzfeld, M, Nachtsheim, C (1996). Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins. J. Cell Sci. 109: 2767-2778 [Abstract]  
• Dahl, U, Sjodin, A, Semb, H (1996). Cadherins regulate aggregation of pancreatic beta-cells in vivo. Development 122: 2895-2902 [Abstract]  
• Leppa, S, Vleminckx, K, Van Roy, F, Jalkanen, M (1996). Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent. J. Cell Sci. 109: 1393-1403 [Abstract]  
• Paulson, A. F., Mooney, E., Fang, X., Ji, H., McCrea, P. D. (2000). Xarvcf, Xenopus Member of the p120 Catenin Subfamily Associating with Cadherin Juxtamembrane Region. J. Biol. Chem. 275: 30124-30131 [Abstract] [Full Text]  
• Deguchi, M., Iizuka, T., Hata, Y., Nishimura, W., Hirao, K., Yao, I., Kawabe, H., Takai, Y. (2000). PAPIN. A NOVEL MULTIPLE PSD-95/Dlg-A/ZO-1 PROTEIN INTERACTING WITH NEURAL PLAKOPHILIN-RELATED Armadillo REPEAT PROTEIN/delta -CATENIN AND p0071. J. Biol. Chem. 275: 29875-29880 [Abstract] [Full Text]  
• Huber, A. H., Stewart, D. B., Laurents, D. V., Nelson, W. J., Weis, W. I. (2001). The Cadherin Cytoplasmic Domain Is Unstructured in the Absence of beta -Catenin. A POSSIBLE MECHANISM FOR REGULATING CADHERIN TURNOVER. J. Biol. Chem. 276: 12301-12309 [Abstract] [Full Text]  
• Omelchenko, T., Fetisova, E., Ivanova, O., Bonder, E. M., Feder, H., Vasiliev, J. M., Gelfand, I. M. (2001). Contact interactions between epitheliocytes and fibroblasts: Formation of heterotypic cadherin-containing adhesion sites is accompanied by local cytoskeletal reorganization. Proc. Natl. Acad. Sci. USA 98: 8632-8637 [Abstract] [Full Text]  
• Calautti, E., Grossi, M., Mammucari, C., Aoyama, Y., Pirro, M., Ono, Y., Li, J., Dotto, G. P. (2002). Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion. JCB 156: 137-148 [Abstract] [Full Text]  
• Horikawa, K., Takeichi, M. (2001). Requirement of the juxtamembrane domain of the cadherin cytoplasmic tail for morphogenetic cell rearrangement during myotome development. JCB 155: 1297-1306 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents