{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:55:14Z","timestamp":1777582514264,"version":"3.51.4"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T00:00:00Z","timestamp":1464912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T00:00:00Z","timestamp":1464912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epithelial-to-mesenchymal transitions (EMT) are strongly implicated in cancer dissemination. Intermediate states, arising from inter-conversion between epithelial (E) and mesenchymal (M) states, are characterized by phenotypic heterogeneity combining E and M features and increased plasticity. Hybrid EMT states are highly relevant in metastatic contexts, but have been largely neglected, partially due to the lack of physiologically-relevant 3D platforms to study them. Here we propose a new <jats:italic>in vitro<\/jats:italic> model, combining mammary E cells with a bioengineered 3D matrix, to explore phenotypic and functional properties of cells in transition between E and M states. Optimized alginate-based 3D matrices provided adequate 3D microenvironments, where normal epithelial morphogenesis was recapitulated, with formation of acini-like structures, similar to those found in native mammary tissue. TGF\u03b21-driven EMT in 3D could be successfully promoted, generating M-like cells. TGF\u03b21 removal resulted in phenotypic switching to an intermediate state (RE cells), a hybrid cell population expressing both E and M markers at gene\/protein levels. RE cells exhibited increased proliferative\/clonogenic activity, as compared to M cells, being able to form large colonies containing cells with front-back polarity, suggesting a more aggressive phenotype. Our 3D model provides a powerful tool to investigate the role of the microenvironment on metastable EMT stages.<\/jats:p>","DOI":"10.1038\/srep27072","type":"journal-article","created":{"date-parts":[[2016,6,3]],"date-time":"2016-06-03T10:14:04Z","timestamp":1464948844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion"],"prefix":"10.1038","volume":"6","author":[{"given":"S. J.","family":"Bidarra","sequence":"first","affiliation":[]},{"given":"P.","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"S.","family":"Rocha","sequence":"additional","affiliation":[]},{"given":"D. P.","family":"Saraiva","sequence":"additional","affiliation":[]},{"given":"C.","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"C. C.","family":"Barrias","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,6,3]]},"reference":[{"key":"BFsrep27072_CR1","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/bcr2416","volume":"11","author":"E Tomaskovic-Crook","year":"2009","unstructured":"Tomaskovic-Crook, E., Thompson, E. W. & Thiery, J. P. Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res 11, 213 (2009).","journal-title":"Breast Cancer Res"},{"key":"BFsrep27072_CR2","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1016\/j.devcel.2008.05.009","volume":"14","author":"J Yang","year":"2008","unstructured":"Yang, J. & Weinberg, R. A. Epithelial-Mesenchymal Transition: At the Crossroads of Development and Tumor Metastasis. Dev Cell 14, 818\u2013829 (2008).","journal-title":"Dev Cell"},{"key":"BFsrep27072_CR3","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/nrc822","volume":"2","author":"JP Thiery","year":"2002","unstructured":"Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2, 442\u2013454 (2002).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep27072_CR4","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","volume":"119","author":"R Kalluri","year":"2009","unstructured":"Kalluri, R. & Weinberg, R. A. The basics of epithelial-mesenchymal transition. J Clinical Invest 119, 1420\u20131428 (2009).","journal-title":"J Clinical Invest"},{"key":"BFsrep27072_CR5","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1016\/j.ccr.2012.11.009","volume":"22","author":"T Brabletz","year":"2012","unstructured":"Brabletz, T. EMT and MET in Metastasis: Where Are the Cancer Stem Cells? Cancer Cell 22, 699\u2013701 (2012).","journal-title":"Cancer Cell"},{"key":"BFsrep27072_CR6","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3389\/fonc.2014.00371","volume":"4","author":"AS Ribeiro","year":"2015","unstructured":"Ribeiro, A. S. & Paredes, J. P-Cadherin Linking Breast Cancer Stem Cells and Invasion: A Promising Marker to Identify an \u201cIntermediate\/Metastable\u201d EMT State. Front Oncol 4, 371 (2015).","journal-title":"Front Oncol"},{"key":"BFsrep27072_CR7","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.2353\/ajpath.2009.080545","volume":"174","author":"MW Klymkowsky","year":"2009","unstructured":"Klymkowsky, M. W. & Savagner, P. Epithelial-Mesenchymal Transition: A Cancer Researcher\u2019s Conceptual Friend and Foe. Am J Pathol 174, 1588\u20131593 (2009).","journal-title":"Am J Pathol"},{"key":"BFsrep27072_CR8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.celrep.2014.12.032","volume":"10","author":"JM Schmidt","year":"2015","unstructured":"Schmidt, J. M. et al. Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation. Cell Rep 10, 131\u2013139 (2015).","journal-title":"Cell Rep"},{"key":"BFsrep27072_CR9","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1126\/science.1203543","volume":"331","author":"CL Chaffer","year":"2011","unstructured":"Chaffer, C. L. & Weinberg, R. A. A Perspective on Cancer Cell Metastasis. Science 331, 1559\u20131564 (2011).","journal-title":"Science"},{"key":"BFsrep27072_CR10","doi-asserted-by":"publisher","first-page":"1891","DOI":"10.2174\/138920111798377021","volume":"12","author":"MA Krasnapolski","year":"2011","unstructured":"Krasnapolski, M. A., Todaro, L. B. & de Kier Joffe, E. B., Is the epithelial-to-mesenchymal transition clinically relevant for the cancer patient? Curr Pharm Biotechnol 12, 1891\u20131899 (2011).","journal-title":"Curr Pharm Biotechnol"},{"key":"BFsrep27072_CR11","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.1228522","volume":"339","author":"M Yu","year":"2013","unstructured":"Yu, M. et al. Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition. Science 339, 580\u2013584 (2013).","journal-title":"Science"},{"key":"BFsrep27072_CR12","doi-asserted-by":"publisher","first-page":"e33191","DOI":"10.1371\/journal.pone.0033191","volume":"7","author":"SS Pinho","year":"2012","unstructured":"Pinho, S. S. et al. Loss and Recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation Is a Mechanism Involved in Epithelial-Mesenchymal-Epithelial Transitions. PLoS ONE 7, e33191 (2012).","journal-title":"PLoS ONE"},{"key":"BFsrep27072_CR13","unstructured":"Olivera, P. et al. Through the looking glass: the reversion of EMT. Eur J Hum Genet 3, Supplement 1 (2015)."},{"key":"BFsrep27072_CR14","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.addr.2015.11.004","volume":"97","author":"LC Roudsari","year":"2016","unstructured":"Roudsari, L. C. & West, J. L., Studying the influence of angiogenesis in in vitro cancer model systems. Adv Drug Deliv Rev 97, 250\u2013259 (2016).","journal-title":"Adv Drug Deliv Rev"},{"key":"BFsrep27072_CR15","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/nrm2236","volume":"8","author":"F Pampaloni","year":"2007","unstructured":"Pampaloni, F., Reynaud, E. G. & Stelzer, E. H. K. The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol 8, 839\u2013845 (2007).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BFsrep27072_CR16","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nmeth1015","volume":"4","author":"GY Lee","year":"2007","unstructured":"Lee, G. Y., Kenny, P. A., Lee, E. H. & Bissell, M. J. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods 4, 359\u2013365 (2007).","journal-title":"Nat Methods"},{"key":"BFsrep27072_CR17","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1002\/bit.22361","volume":"103","author":"MW Tibbitt","year":"2009","unstructured":"Tibbitt, M. W. & Anseth, K. S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103, 655\u2013663 (2009).","journal-title":"Biotechnol Bioeng"},{"key":"BFsrep27072_CR18","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1016\/j.jbiomech.2013.09.029","volume":"47","author":"BJ Gill","year":"2014","unstructured":"Gill, B. J. & West, J. L. Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology. J Biomech 47, 1969\u20131978 (2014).","journal-title":"J Biomech"},{"key":"BFsrep27072_CR19","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nmeth1085","volume":"4","author":"C Fischbach","year":"2007","unstructured":"Fischbach, C. et al. Engineering tumors with 3D scaffolds. Nat Methods 4, 855\u2013860 (2007).","journal-title":"Nat Methods"},{"key":"BFsrep27072_CR20","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/nrc3564","volume":"13","author":"MH Zaman","year":"2013","unstructured":"Zaman, M. H. The role of engineering approaches in analysing cancer invasion and metastasis. Nat Rev Cancer 13, 596\u2013603 (2013).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep27072_CR21","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/494131a","volume":"494","author":"V Marx","year":"2013","unstructured":"Marx, V. Tracking metastasis and tricking cancer. Nature 494, 133\u2013138 (2013).","journal-title":"Nature"},{"key":"BFsrep27072_CR22","doi-asserted-by":"publisher","first-page":"6013","DOI":"10.1158\/0008-5472.CAN-12-0895","volume":"72","author":"BJ Gill","year":"2012","unstructured":"Gill, B. J. et al. A Synthetic Matrix with Independently Tunable Biochemistry and Mechanical Properties to Study Epithelial Morphogenesis and EMT in a Lung Adenocarcinoma Model. Cancer Res 72, 6013\u20136023 (2012).","journal-title":"Cancer Res"},{"key":"BFsrep27072_CR23","doi-asserted-by":"publisher","first-page":"7897","DOI":"10.1016\/j.biomaterials.2011.07.013","volume":"32","author":"SJ Bidarra","year":"2011","unstructured":"Bidarra, S. J. et al. Injectable in situ crosslinkable RGD-modified alginate matrix for endothelial cells delivery. Biomaterials 32, 7897\u20137904 (2011).","journal-title":"Biomaterials"},{"key":"BFsrep27072_CR24","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1016\/j.actbio.2014.02.049","volume":"10","author":"FR Maia","year":"2014","unstructured":"Maia, F. R. et al. Matrix-driven formation of mesenchymal stem cell-extracellular matrix microtissues on soft alginate hydrogels. Acta Biomater 10, 3197\u20133208 (2014).","journal-title":"Acta Biomater"},{"key":"BFsrep27072_CR25","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nmat2732","volume":"9","author":"N Huebsch","year":"2010","unstructured":"Huebsch, N. et al. Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate. Nat Mater 9, 518\u2013526 (2010).","journal-title":"Nat Mater"},{"key":"BFsrep27072_CR26","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nrc2544","volume":"9","author":"DT Butcher","year":"2009","unstructured":"Butcher, D. T., Alliston, T. & Weaver, V. M. A tense situation: forcing tumour progression. Nat Rev Cancer 9, 108\u2013122 (2009).","journal-title":"Nat Rev Cancer"},{"key":"BFsrep27072_CR27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.ccr.2005.08.010","volume":"8","author":"MJ Paszek","year":"2005","unstructured":"Paszek, M. J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241\u2013254 (2005).","journal-title":"Cancer Cell"},{"key":"BFsrep27072_CR28","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.cell.2009.10.027","volume":"139","author":"KR Levental","year":"2009","unstructured":"Levental, K. R. et al. Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin signaling. Cell 139, 891\u2013906 (2009).","journal-title":"Cell"},{"key":"BFsrep27072_CR29","doi-asserted-by":"publisher","first-page":"3548","DOI":"10.1016\/j.biomaterials.2012.01.055","volume":"33","author":"MS Weiss","year":"2012","unstructured":"Weiss, M. S. et al. The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells. Biomaterials 33, 3548\u20133559 (2012).","journal-title":"Biomaterials"},{"key":"BFsrep27072_CR30","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.2147\/IJN.S66723","volume":"10","author":"K Mi","year":"2015","unstructured":"Mi, K. & Xing, Z. CD44(+)\/CD24(\u2212) breast cancer cells exhibit phenotypic reversion in three-dimensional self-assembling peptide RADA16 nanofiber scaffold. Int J Nanomedicine 10, 3043\u20133053 (2015).","journal-title":"Int J Nanomedicine"},{"key":"BFsrep27072_CR31","doi-asserted-by":"publisher","first-page":"e71273","DOI":"10.1371\/journal.pone.0071273","volume":"8","author":"S Li","year":"2013","unstructured":"Li, S. et al. Cell Surface Glycan Alterations in Epithelial Mesenchymal Transition Process of Huh7 Hepatocellular Carcinoma Cell. PLoS ONE 8, e71273 (2013).","journal-title":"PLoS ONE"},{"key":"BFsrep27072_CR32","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.1128\/MCB.24.10.4241-4254.2004","volume":"24","author":"M Kowanetz","year":"2004","unstructured":"Kowanetz, M. et al. Id2 and Id3 Define the Potency of Cell Proliferation and Differentiation Responses to Transforming Growth Factor beta and Bone Morphogenetic Protein. Mol Cell Biol 24, 4241\u20134254 (2004).","journal-title":"Mol Cell Biol"},{"key":"BFsrep27072_CR33","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10911-010-9177-x","volume":"15","author":"ES Radisky","year":"2010","unstructured":"Radisky, E. S. & Radisky, D. C. Matrix Metalloproteinase-Induced Epithelial-Mesenchymal Transition in Breast Cancer. J Mammary Gland Biol Neoplasia 15, 201\u2013212 (2010).","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"BFsrep27072_CR34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3389\/fcell.2015.00004","volume":"3","author":"A Jacob","year":"2015","unstructured":"Jacob, A. & Prekeris, R. The regulation of MMP targeting to invadopodia during cancer metastasis. Front Cell Dev Biol 3, 4 (2015).","journal-title":"Front Cell Dev Biol"},{"key":"BFsrep27072_CR35","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.molonc.2007.02.004","volume":"1","author":"PA Kenny","year":"2007","unstructured":"Kenny, P. A. et al. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol Oncol 1, 84\u201396 (2007).","journal-title":"Mol Oncol"},{"key":"BFsrep27072_CR36","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1002\/ijc.25781","volume":"128","author":"G Benton","year":"2011","unstructured":"Benton, G., Kleinman, H. K., George, J. & Arnaoutova, I. Multiple uses of basement membrane-like matrix (BME\/Matrigel) in vitro and in vivo with cancer cells. Int J Cancer 128, 1751\u20137 (2011).","journal-title":"Int J Cancer"},{"key":"BFsrep27072_CR37","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1007\/s11626-998-0080-3","volume":"34","author":"R Montesano","year":"1998","unstructured":"Montesano, R., Soriano, J. V., Fialka, I. & Orci, L. Isolation of EpH4 mammary epithelial cell subpopulations which differ in their morphogenetic properties. In Vitro Cell Dev Biol Anim 34, 468\u2013477 (1998).","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"BFsrep27072_CR38","doi-asserted-by":"publisher","first-page":"18144","DOI":"10.1073\/pnas.1318192110","volume":"110","author":"M Lu","year":"2013","unstructured":"Lu, M. et al. MicroRNA-based regulation of epithelial-hybrid-mesenchymal fate determination. Proc Nati Acad Sci USA 110, 18144\u201318149 (2013).","journal-title":"Proc Nati Acad Sci USA"},{"key":"BFsrep27072_CR39","doi-asserted-by":"publisher","first-page":"11271","DOI":"10.1158\/0008-5472.CAN-06-2044","volume":"66","author":"CL Chaffer","year":"2006","unstructured":"Chaffer, C. L. et al. Mesenchymal-to-Epithelial Transition Facilitates Bladder Cancer Metastasis: Role of Fibroblast Growth Factor Receptor-2. Cancer Res 66, 11271\u201311278 (2006).","journal-title":"Cancer Res"},{"key":"BFsrep27072_CR40","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nm.2401","volume":"17","author":"M Korpal","year":"2012","unstructured":"Korpal, M. et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17, 1101\u20131108 (2012).","journal-title":"Nat Med"},{"key":"BFsrep27072_CR41","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1016\/j.biomaterials.2004.06.044","volume":"26","author":"T Boontheekul","year":"2005","unstructured":"Boontheekul, T., Kong, H.-J. & Mooney, D. J. Controlling alginate gel degradation utilizing partial oxidation and bimodal molecular weight distribution. Biomaterials 26, 2455\u20132465 (2005).","journal-title":"Biomaterials"},{"key":"BFsrep27072_CR42","doi-asserted-by":"publisher","first-page":"4097","DOI":"10.1091\/mbc.e12-02-0166","volume":"23","author":"K Lee","year":"2012","unstructured":"Lee, K. et al. Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial-mesenchymal transition. Mol Biol Cell 23, 4097\u20134108 (2012).","journal-title":"Mol Biol Cell"},{"key":"BFsrep27072_CR43","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/ncb3157","volume":"17","author":"SC Wei","year":"2015","unstructured":"Wei, S. C. et al. Matrix stiffness drives epithelial-mesenchymal transition and tumour metastasis through a TWIST1-G3BP2 mechanotransduction pathway. Nat Cell Biol 17, 678\u2013688 (2015).","journal-title":"Nat Cell Biol"},{"key":"BFsrep27072_CR44","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.bbrc.2010.08.073","volume":"400","author":"A Aguirre","year":"2010","unstructured":"Aguirre, A., Planell, J. A. & Engel, E. Dynamics of bone marrow-derived endothelial progenitor cell\/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis. Biochem Biophys Res Commun 400, 284\u2013291 (2010).","journal-title":"Biochem Biophys Res Commun"},{"key":"BFsrep27072_CR45","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.tcb.2011.06.005","volume":"21","author":"LM McCaffrey","year":"2011","unstructured":"McCaffrey, L. M. & Macara, I. G. Epithelial organization, cell polarity and tumorigenesis. Trends Cell Biol 21, 727\u2013735 (2011).","journal-title":"Trends Cell Biol"},{"key":"BFsrep27072_CR46","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1038\/nmat4009","volume":"13","author":"O Chaudhuri","year":"2014","unstructured":"Chaudhuri, O. et al. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat Mater 13, 970\u2013978 (2014).","journal-title":"Nat Mater"},{"key":"BFsrep27072_CR47","doi-asserted-by":"publisher","first-page":"4326","DOI":"10.1038\/onc.2009.299","volume":"28","author":"PP Provenzano","year":"2009","unstructured":"Provenzano, P. P., Inman, D. R., Eliceiri, K. W. & Keely, P. J. Matrix density-induced mechanoregulation of breast cell phenotype, signaling, and gene expression through a FAK-ERK linkage. Oncogene 28, 4326\u20134343 (2009).","journal-title":"Oncogene"},{"key":"BFsrep27072_CR48","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.yexcr.2013.03.035","volume":"319","author":"L Foroni","year":"2013","unstructured":"Foroni, L. et al. The role of 3D microenvironmental organization in MCF-7 epithelial-mesenchymal transition after 7 culture days. Exp Cell Res 319, 1515\u20131522 (2013).","journal-title":"Exp Cell Res"},{"key":"BFsrep27072_CR49","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/onc.2015.133","volume":"35","author":"MF Pang","year":"2016","unstructured":"Pang, M. F. et al. TGF-[beta]1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7\/CCL21-mediated chemotaxis. Oncogene 35, 748\u2013760 (2016).","journal-title":"Oncogene"},{"key":"BFsrep27072_CR50","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/cr.2009.5","volume":"19","author":"J Xu","year":"2009","unstructured":"Xu, J., Lamouille, S. & Derynck, R. TGF-[beta]-induced epithelial to mesenchymal transition. Cell Res 19, 156\u2013172 (2009).","journal-title":"Cell Res"},{"key":"BFsrep27072_CR51","doi-asserted-by":"publisher","first-page":"16563","DOI":"10.1074\/jbc.M111.262154","volume":"287","author":"Q Xu","year":"2012","unstructured":"Xu, Q. et al. Roles of N-Acetylglucosaminyltransferase III in Epithelial-to-Mesenchymal Transition Induced by Transforming Growth Factor beta1 (TGF-beta1) in Epithelial Cell Lines. J Biol Chem 287, 16563\u201316574 (2012).","journal-title":"J Biol Chem"},{"key":"BFsrep27072_CR52","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1038\/sj.cdd.4401467","volume":"11","author":"M Kondo","year":"2004","unstructured":"Kondo, M. et al. A role for Id in the regulation of TGF-[beta]-induced epithelial-mesenchymal transdifferentiation. Cell Death Differ 11, 1092\u20131101 (2004).","journal-title":"Cell Death Differ"},{"key":"BFsrep27072_CR53","doi-asserted-by":"publisher","first-page":"3795","DOI":"10.1128\/MCB.00434-13","volume":"33","author":"C Chang","year":"2012","unstructured":"Chang, C., Yang, X., Pursell, B. & Mercurio, A. M. Id2 Complexes with the SNAG Domain of Snai1 Inhibiting Snai1-Mediated Repression of Integrin beta4. Mol Cell Biol 33, 3795\u20133804 (2012).","journal-title":"Mol Cell Biol"},{"key":"BFsrep27072_CR54","doi-asserted-by":"publisher","first-page":"5764","DOI":"10.1038\/sj.onc.1208927","volume":"24","author":"J Zavadil","year":"2005","unstructured":"Zavadil, J. & Bottinger, E. P. TGF-[beta] and epithelial-to-mesenchymal transitions. Oncogene 24, 5764\u20135774 (2005).","journal-title":"Oncogene"},{"key":"BFsrep27072_CR55","doi-asserted-by":"publisher","first-page":"233","DOI":"10.4161\/19336918.2014.983794","volume":"9","author":"EJ Tan","year":"2015","unstructured":"Tan, E. J., Olsson, A.-K. & Moustakas, A. Reprogramming during epithelial to mesenchymal transition under the control of TGF\u03b2. Cell Adh Migr 9, 233\u2013246 (2015).","journal-title":"Cell Adh Migr"},{"key":"BFsrep27072_CR56","doi-asserted-by":"publisher","first-page":"10356","DOI":"10.1073\/pnas.171610498","volume":"98","author":"T Brabletz","year":"2001","unstructured":"Brabletz, T. et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Nati Acad Sci USA 98, 10356\u201310361 (2001).","journal-title":"Proc Nati Acad Sci USA"},{"key":"BFsrep27072_CR57","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1158\/1541-7786.MCR-11-0371","volume":"9","author":"DD Tran","year":"2011","unstructured":"Tran, D. D. et al. Temporal and Spatial Cooperation of Snail1 and Twist1 during Epithelial-Mesenchymal Transition Predicts for Human Breast Cancer Recurrence. Mol Cancer Res 9, 1644\u20131657 (2011).","journal-title":"Mol Cancer Res"},{"key":"BFsrep27072_CR58","doi-asserted-by":"publisher","first-page":"e16186","DOI":"10.1371\/journal.pone.0016186","volume":"6","author":"R Strauss","year":"2011","unstructured":"Strauss, R. et al. Analysis of Epithelial and Mesenchymal Markers in Ovarian Cancer Reveals Phenotypic Heterogeneity and Plasticity. PLoS ONE 6, e16186 (2011).","journal-title":"PLoS ONE"},{"key":"BFsrep27072_CR59","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1158\/0008-5472.CAN-14-3476","volume":"75","author":"M Ruscetti","year":"2015","unstructured":"Ruscetti, M. et al. Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis. Cancer Res 75, 2749\u20132759 (2015).","journal-title":"Cancer Res"},{"key":"BFsrep27072_CR60","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.4161\/cc.10.17.17188","volume":"10","author":"NV Jordan","year":"2011","unstructured":"Jordan, N. V., Johnson, G. L. & Abell, A. N. Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle 10, 2865\u20132873 (2011).","journal-title":"Cell Cycle"},{"key":"BFsrep27072_CR61","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S0142-9612(98)00107-0","volume":"20","author":"JA Rowley","year":"1999","unstructured":"Rowley, J. A., Madlambayan, G. & Mooney, D. J. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20, 45\u201353 (1999).","journal-title":"Biomaterials"},{"key":"BFsrep27072_CR62","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1016\/j.actbio.2010.12.029","volume":"7","author":"K Fonseca","year":"2011","unstructured":"Fonseca, K. et al. Molecularly-designed alginate hydrogels susceptible to local proteolysis as 3D cellular microenvironments. Acta Biomater 7, 1674\u20131682 (2011).","journal-title":"Acta Biomater"},{"key":"BFsrep27072_CR63","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2-[Delta][Delta]CT Method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep27072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27072","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep27072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T05:11:30Z","timestamp":1672895490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep27072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,3]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,6,29]]}},"alternative-id":["BFsrep27072"],"URL":"https:\/\/doi.org\/10.1038\/srep27072","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,3]]},"assertion":[{"value":"10 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27072"}}