{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:28:11Z","timestamp":1789079291239,"version":"build-2803163510"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:00:00Z","timestamp":1578009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:00:00Z","timestamp":1578009600000},"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":["Cell Mol Immunol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thymic involution during aging is a major cause of decreased T-cell production and reduced immunity. Here, we show that the loss of CD147 on T cells prevents thymic senescence, resulting in slowed shrinkage of the thymus with age and increased production of naive T cells. This phenotype is the result of slowing of the epithelial\u2013mesenchymal transition (EMT) process in thymic epithelial cells (TECs), which eventually leads to reduced adipocyte accumulation. In an in vitro coculture system, we found that TGF\u03b2 is an important factor in the EMT process in TECs and that it can reduce the expression of E-cadherin through p-Smad2\/FoxC2 signaling. Moreover, CD147 on T cells can accelerate the decline in E-cadherin expression by interacting with Annexin A2 on TECs. In the presence of TGF\u03b2, Annexin A2 and E-cadherin colocalize on TECs. However, CD147 on T cells competitively binds to Annexin A2 on TECs, leading to the isolation of E-cadherin. Then, the isolated E-cadherin is easily phosphorylated by phosphorylated Src kinase, the phosphorylation of which was induced by TGF\u03b2, and finally, p-E-cadherin is degraded. Thus, in the thymus, the interaction between T cells and TECs contributes to thymic involution with age. In this study, we illuminate the mechanism underlying the triggering of the EMT process in TECs and show that inhibiting TGF\u03b2 and\/or CD147 may serve as a strategy to hinder age-related thymic involution.<\/jats:p>","DOI":"10.1038\/s41423-019-0353-7","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T09:02:44Z","timestamp":1578042164000},"page":"171-181","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["CD147 deficiency in T cells prevents thymic involution by inhibiting the EMT process in TECs in the presence of TGF\u03b2"],"prefix":"10.1038","volume":"18","author":[{"given":"Ruo","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Jie","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Nan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,3]]},"reference":[{"key":"353_CR1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nri2993","volume":"11","author":"JF Miller","year":"2011","unstructured":"Miller, J. F. The golden anniversary of the thymus. Nat. Rev. Immunol. 11, 489\u2013495 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"353_CR2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/ni.1887","volume":"11","author":"AC Carpenter","year":"2010","unstructured":"Carpenter, A. C. & Bosselut, R. Decision checkpoints in the thymus. Nat. Immunol. 11, 666\u2013673 (2010).","journal-title":"Nat. Immunol."},{"key":"353_CR3","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.coi.2008.03.001","volume":"20","author":"T Boehm","year":"2008","unstructured":"Boehm, T. Thymus development and function. Curr. Opin. Immunol. 20, 178\u2013184 (2008).","journal-title":"Curr. Opin. Immunol."},{"key":"353_CR4","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nri3534","volume":"13","author":"T Boehm","year":"2013","unstructured":"Boehm, T. & Swann, J. B. Thymus involution and regeneration: Two sides of the same coin? Nat. Rev. Immunol. 13, 831\u2013838 (2013).","journal-title":"Nat. Rev. Immunol."},{"key":"353_CR5","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev.immunol.26.021607.090408","volume":"26","author":"HR Rodewald","year":"2008","unstructured":"Rodewald, H. R. Thymus organogenesis. Annu Rev. Immunol. 26, 355\u2013388 (2008).","journal-title":"Annu Rev. Immunol."},{"key":"353_CR6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.thorsurg.2018.12.001","volume":"29","author":"P Thapa","year":"2019","unstructured":"Thapa, P. & Farber, D. L. The role of the thymus in the immune response. Thorac. Surg. Clin. 29, 123\u2013131 (2019).","journal-title":"Thorac. Surg. Clin."},{"key":"353_CR7","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.it.2009.04.003","volume":"30","author":"HE Lynch","year":"2009","unstructured":"Lynch, H. E. et al. Thymic involution and immune reconstitution. Trends Immunol. 30, 366\u2013373 (2009).","journal-title":"Trends Immunol."},{"key":"353_CR8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/path.2104","volume":"211","author":"AL Gruver","year":"2007","unstructured":"Gruver, A. L., Hudson, L. L. & Sempowski, G. D. Immunosenescence of ageing. J. Pathol. 211, 144\u2013156 (2007).","journal-title":"J. Pathol."},{"key":"353_CR9","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.4049\/jimmunol.164.4.2180","volume":"164","author":"GD Sempowski","year":"2000","unstructured":"Sempowski, G. D. et al. Leukemia inhibitory factor, oncostatin m, il-6, and stem cell factor mRNA expression in human thymus increases with age and is associated with thymic atrophy. J. Immunol. 164, 2180\u20132187 (2000).","journal-title":"J. Immunol."},{"key":"353_CR10","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.2741\/3866","volume":"16","author":"NR Manley","year":"2011","unstructured":"Manley, N. R., Richie, E. R., Blackburn, C. C., Condie, B. G. & Sage, J. Structure and function of the thymic microenvironment. Front Biosci. (Landmark Ed.) 16, 2461\u20132477 (2011).","journal-title":"Front Biosci. (Landmark Ed.)"},{"key":"353_CR11","first-page":"437","volume":"2","author":"D Aw","year":"2011","unstructured":"Aw, D. & Palmer, D. B. The origin and implication of thymic involution. Aging Dis. 2, 437\u2013443 (2011).","journal-title":"Aging Dis."},{"key":"353_CR12","first-page":"1085","volume":"118","author":"LA Napolitano","year":"2008","unstructured":"Napolitano, L. A. et al. Growth hormone enhances thymic function in hiv-1-infected adults. J. Clin. Investig. 118, 1085\u20131098 (2008).","journal-title":"J. Clin. Investig."},{"key":"353_CR13","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1084\/jem.20121716","volume":"210","author":"PM Garfin","year":"2013","unstructured":"Garfin, P. M. et al. Inactivation of the rb family prevents thymus involution and promotes thymic function by direct control of foxn1 expression. J. Exp. Med. 210, 1087\u20131097 (2013).","journal-title":"J. Exp. Med."},{"key":"353_CR14","doi-asserted-by":"crossref","first-page":"7068","DOI":"10.1074\/jbc.M808302200","volume":"284","author":"YH Youm","year":"2009","unstructured":"Youm, Y. H. et al. Deficient ghrelin receptor-mediated signaling compromises thymic stromal cell microenvironment by accelerating thymic adiposity. J. Biol. Chem. 284, 7068\u20137077 (2009).","journal-title":"J. Biol. Chem."},{"key":"353_CR15","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.4049\/jimmunol.0900562","volume":"183","author":"H Yang","year":"2009","unstructured":"Yang, H., Youm, Y. H. & Dixit, V. D. Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution. J. Immunol. 183, 3040\u20133052 (2009).","journal-title":"J. Immunol."},{"key":"353_CR16","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.3389\/fimmu.2017.01515","volume":"8","author":"D Ernszt","year":"2017","unstructured":"Ernszt, D. et al. Ppargamma deficiency counteracts thymic senescence. Front. Immunol. 8, 1515 (2017).","journal-title":"Front. Immunol."},{"key":"353_CR17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.semcdb.2014.02.008","volume":"29","author":"KL Fok","year":"2014","unstructured":"Fok, K. L., Chen, H., Ruan, Y. C. & Chan, H. C. Novel regulators of spermatogenesis. Semin Cell Dev. Biol. 29, 31\u201342 (2014).","journal-title":"Semin Cell Dev. Biol."},{"key":"353_CR18","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.matbio.2015.01.018","volume":"44-46","author":"DK Kaushik","year":"2015","unstructured":"Kaushik, D. K., Hahn, J. N. & Yong, V. W. Emmprin, an upstream regulator of mmps, in cns biology. Matrix Biol. 44-46, 138\u2013146 (2015).","journal-title":"Matrix Biol."},{"key":"353_CR19","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1055\/s-0034-1390001","volume":"40","author":"GJ Pennings","year":"2014","unstructured":"Pennings, G. J. & Kritharides, L. Cd147 in cardiovascular disease and thrombosis. Semin Thromb. Hemost. 40, 747\u2013755 (2014).","journal-title":"Semin Thromb. Hemost."},{"key":"353_CR20","doi-asserted-by":"crossref","first-page":"17411","DOI":"10.3390\/ijms151017411","volume":"15","author":"L Xiong","year":"2014","unstructured":"Xiong, L., Edwards, C. K. 3rd & Zhou, L. The biological function and clinical utilization of cd147 in human diseases: A review of the current scientific literature. Int. J. Mol. Sci. 15, 17411\u201317441 (2014).","journal-title":"Int. J. Mol. Sci."},{"key":"353_CR21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s10585-014-9689-7","volume":"32","author":"Y Wang","year":"2015","unstructured":"Wang, Y. et al. A chimeric antibody targeting cd147 inhibits hepatocellular carcinoma cell motility via fak-pi3k-akt-girdin signaling pathway. Clin. Exp. Metastasis 32, 39\u201353 (2015).","journal-title":"Clin. Exp. Metastasis"},{"key":"353_CR22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/cbin.10341","volume":"39","author":"NY Ru","year":"2015","unstructured":"Ru, N. Y., Wu, J., Chen, Z. N. & Bian, H. Hab18g\/cd147 is involved in tgf-beta-induced epithelial-mesenchymal transition and hepatocellular carcinoma invasion. Cell Biol. Int 39, 44\u201351 (2015).","journal-title":"Cell Biol. Int"},{"key":"353_CR23","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1182\/blood-2017-08-802918","volume":"131","author":"MY Zhang","year":"2018","unstructured":"Zhang, M. Y. et al. Disrupting cd147-rap2 interaction abrogates erythrocyte invasion by plasmodium falciparum. Blood 131, 1111\u20131121 (2018).","journal-title":"Blood"},{"key":"353_CR24","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4196\/kjpp.2016.20.5.515","volume":"20","author":"MY Kim","year":"2016","unstructured":"Kim, M. Y. & Cho, J. Y. Molecular association of cd98, cd29, and cd147 critically mediates monocytic u937 cell adhesion. Korean J. Physiol. Pharm. 20, 515\u2013523 (2016).","journal-title":"Korean J. Physiol. Pharm."},{"key":"353_CR25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1365-2567.2005.02316.x","volume":"117","author":"V Yurchenko","year":"2006","unstructured":"Yurchenko, V., Constant, S. & Bukrinsky, M. Dealing with the family: Cd147 interactions with cyclophilins. Immunology 117, 301\u2013309 (2006).","journal-title":"Immunology"},{"key":"353_CR26","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/hep.29798","volume":"68","author":"M Lu","year":"2018","unstructured":"Lu, M. et al. Basolateral cd147 induces hepatocyte polarity loss by e-cadherin ubiquitination and degradation in hepatocellular carcinoma progress. Hepatology 68, 317\u2013332 (2018).","journal-title":"Hepatology"},{"key":"353_CR27","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1038\/onc.2011.149","volume":"30","author":"J Wu","year":"2011","unstructured":"Wu, J. et al. Hab18g\/cd147 promotes epithelial-mesenchymal transition through tgf-beta signaling and is transcriptionally regulated by slug. Oncogene 30, 4410\u20134427 (2011).","journal-title":"Oncogene"},{"key":"353_CR28","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/s41423-018-0012-4","volume":"16","author":"N Guo","year":"2019","unstructured":"Guo, N. et al. A critical epitope in cd147 facilitates memory cd4(+) t-cell hyper-activation in rheumatoid arthritis. Cell. Mol. Immunol. 16, 568\u2013579 (2019).","journal-title":"Cell. Mol. Immunol."},{"key":"353_CR29","doi-asserted-by":"publisher","unstructured":"Dong X. et al. Acpas promote il-1beta production in rheumatoid arthritis by activating the nlrp3 inflammasome. Cell. Mol. Immunol. 2019. https:\/\/doi.org\/10.1038\/s41423-019-0201-9.","DOI":"10.1038\/s41423-019-0201-9"},{"key":"353_CR30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/j.1399-0039.1997.tb02853.x","volume":"50","author":"AH Kirsch","year":"1997","unstructured":"Kirsch, A. H., Diaz, L. A. Jr., Bonish, B., Antony, P. A. & Fox, D. A. The pattern of expression of cd147\/neurothelin during human t-cell ontogeny as defined by the monoclonal antibody 8d6. Tissue Antigens 50, 147\u2013152 (1997).","journal-title":"Tissue Antigens"},{"key":"353_CR31","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.4049\/jimmunol.168.10.4946","volume":"168","author":"T Renno","year":"2002","unstructured":"Renno, T. et al. A role for cd147 in thymic development. J. Immunol. 168, 4946\u20134950 (2002).","journal-title":"J. Immunol."},{"key":"353_CR32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.7150\/ijbs.6818","volume":"10","author":"H Yao","year":"2013","unstructured":"Yao, H. et al. Important functional roles of basigin in thymocyte development and t cell activation. Int J. Biol. Sci. 10, 43\u201352 (2013).","journal-title":"Int J. Biol. Sci."},{"key":"353_CR33","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ebiom.2017.05.022","volume":"20","author":"JJ Geng","year":"2017","unstructured":"Geng, J. J. et al. Targeting cd147 for t to nk lineage reprogramming and tumor therapy. EBioMedicine 20, 98\u2013108 (2017).","journal-title":"EBioMedicine"},{"key":"353_CR34","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.it.2012.03.005","volume":"33","author":"G Anderson","year":"2012","unstructured":"Anderson, G. & Takahama, Y. Thymic epithelial cells: Working class heroes for t cell development and repertoire selection. Trends Immunol. 33, 256\u2013263 (2012).","journal-title":"Trends Immunol."},{"key":"353_CR35","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1084\/jem.173.5.1039","volume":"173","author":"DB Agus","year":"1991","unstructured":"Agus, D. B., Surh, C. D. & Sprent, J. Reentry of t cells to the adult thymus is restricted to activated t cells. J. Exp. Med. 173, 1039\u20131046 (1991).","journal-title":"J. Exp. Med."},{"key":"353_CR36","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1111\/j.1582-4934.2010.01012.x","volume":"14","author":"J Hu","year":"2010","unstructured":"Hu, J. et al. Involvement of hab18g\/cd147 in t cell activation and immunological synapse formation. J. Cell Mol. Med 14, 2132\u20132143 (2010).","journal-title":"J. Cell Mol. Med"},{"key":"353_CR37","volume":"7","author":"C Yin","year":"2017","unstructured":"Yin, C. et al. Thymic homing of activated cd4(+) t cells induces degeneration of the thymic epithelium through excessive rank signaling. Sci. Rep. 7, 2421 (2017).","journal-title":"Sci. Rep."},{"key":"353_CR38","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4143\/crt.2017.613","volume":"51","author":"J Cai","year":"2019","unstructured":"Cai, J. et al. Tumor-associated macrophages derived tgf-betainduced epithelial to mesenchymal transition in colorectal cancer cells through smad2,3-4\/snail signaling pathway. Cancer Res. Treat. 51, 252\u2013266 (2019).","journal-title":"Cancer Res. Treat."},{"key":"353_CR39","volume":"8","author":"MR Rocha","year":"2018","unstructured":"Rocha, M. R. et al. Annexin a2 overexpression associates with colorectal cancer invasiveness and tgf-ss induced epithelial mesenchymal transition via src\/anxa2\/stat3. Sci. Rep. 8, 11285 (2018).","journal-title":"Sci. Rep."},{"key":"353_CR40","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.smim.2012.04.005","volume":"24","author":"IK Chinn","year":"2012","unstructured":"Chinn, I. K., Blackburn, C. C., Manley, N. R. & Sempowski, G. D. Changes in primary lymphoid organs with aging. Semin. Immunol. 24, 309\u2013320 (2012).","journal-title":"Semin. Immunol."},{"key":"353_CR41","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.coi.2013.06.002","volume":"25","author":"MS Ventevogel","year":"2013","unstructured":"Ventevogel, M. S. & Sempowski, G. D. Thymic rejuvenation and aging. Curr. Opin. Immunol. 25, 516\u2013522 (2013).","journal-title":"Curr. Opin. Immunol."},{"key":"353_CR42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.anndiagpath.2003.11.006","volume":"8","author":"LP Hale","year":"2004","unstructured":"Hale, L. P. Histologic and molecular assessment of human thymus. Ann. Diagn. Pathol. 8, 50\u201360 (2004).","journal-title":"Ann. Diagn. Pathol."},{"key":"353_CR43","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0145-305X(00)00071-9","volume":"25","author":"LP Hale","year":"2001","unstructured":"Hale, L. P., Clark, A. G., Li, J., Greer, P. K. & Byers Kraus, V. Age-related thymic atrophy in the guinea pig. Dev. Comp. Immunol. 25, 509\u2013518 (2001).","journal-title":"Dev. Comp. Immunol."},{"key":"353_CR44","doi-asserted-by":"crossref","first-page":"e10701","DOI":"10.1371\/journal.pone.0010701","volume":"5","author":"K Kvell","year":"2010","unstructured":"Kvell, K. et al. Wnt4 and lap2alpha as pacemakers of thymic epithelial senescence. PLoS ONE 5, e10701 (2010).","journal-title":"PLoS ONE"},{"key":"353_CR45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1242\/dev.111.1.117","volume":"111","author":"P Schmid","year":"1991","unstructured":"Schmid, P., Cox, D., Bilbe, G., Maier, R. & McMaster, G. K. Differential expression of tgf beta 1, beta 2 and beta 3 genes during mouse embryogenesis. Development 111, 117\u2013130 (1991).","journal-title":"Development"},{"key":"353_CR46","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1196\/annals.1254.031","volume":"998","author":"P Bernasconi","year":"2003","unstructured":"Bernasconi, P. et al. Expression of transforming growth factor-beta1 in thymus of myasthenia gravis patients: Correlation with pathological abnormalities. Ann. N. Y Acad. Sci. 998, 278\u2013283 (2003).","journal-title":"Ann. N. Y Acad. Sci."},{"key":"353_CR47","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1182\/blood-2007-10-115618","volume":"112","author":"MM Hauri-Hohl","year":"2008","unstructured":"Hauri-Hohl, M. M. et al. Tgf-beta signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution. Blood 112, 626\u2013634 (2008).","journal-title":"Blood"},{"key":"353_CR48","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/ni.2869","volume":"15","author":"M Hauri-Hohl","year":"2014","unstructured":"Hauri-Hohl, M., Zuklys, S., Hollander, G. A. & Ziegler, S. F. A regulatory role for tgf-beta signaling in the establishment and function of the thymic medulla. Nat. Immunol. 15, 554\u2013561 (2014).","journal-title":"Nat. Immunol."},{"key":"353_CR49","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/intimm\/dxt026","volume":"25","author":"C Odaka","year":"2013","unstructured":"Odaka, C. et al. Tgf-beta type ii receptor expression in thymic epithelial cells inhibits the development of hassall's corpuscles in mice. Int. Immunol. 25, 633\u2013642 (2013).","journal-title":"Int. Immunol."},{"key":"353_CR50","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ydbio.2006.06.012","volume":"296","author":"S Seo","year":"2006","unstructured":"Seo, S. & Kume, T. Forkhead transcription factors, foxc1 and foxc2, are required for the morphogenesis of the cardiac outflow tract. Dev. Biol. 296, 421\u2013436 (2006).","journal-title":"Dev. Biol."},{"key":"353_CR51","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ydbio.2006.03.035","volume":"294","author":"S Seo","year":"2006","unstructured":"Seo, S. et al. The forkhead transcription factors, foxc1 and foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev. Biol. 294, 458\u2013470 (2006).","journal-title":"Dev. Biol."},{"key":"353_CR52","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1083\/jcb.200901104","volume":"185","author":"C Norrmen","year":"2009","unstructured":"Norrmen, C. et al. Foxc2 controls formation and maturation of lymphatic collecting vessels through cooperation with nfatc1. J. Cell Biol. 185, 439\u2013457 (2009).","journal-title":"J. Cell Biol."},{"key":"353_CR53","first-page":"415","volume":"36","author":"M Katoh","year":"2010","unstructured":"Katoh, M. & Katoh, M. Integrative genomic analyses of cxcr4: Transcriptional regulation of cxcr4 based on tgfbeta, nodal, activin signaling and pou5f1, foxa2, foxc2, foxh1, sox17, and gfi1 transcription factors. Int J. Oncol. 36, 415\u2013420 (2010).","journal-title":"Int J. Oncol."},{"key":"353_CR54","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.3892\/or.2014.3119","volume":"31","author":"B Liu","year":"2014","unstructured":"Liu, B., Han, S. M., Tang, X. Y., Han, L. & Li, C. Z. Overexpressed foxc2 in ovarian cancer enhances the epithelial-to-mesenchymal transition and invasion of ovarian cancer cells. Oncol. Rep. 31, 2545\u20132554 (2014).","journal-title":"Oncol. Rep."},{"key":"353_CR55","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1002\/hep.24592","volume":"54","author":"P Zhao","year":"2011","unstructured":"Zhao, P. et al. Hab18g\/cd147 promotes cell motility by regulating annexin ii-activated rhoa and rac1 signaling pathways in hepatocellular carcinoma cells. Hepatology 54, 2012\u20132024 (2011).","journal-title":"Hepatology"}],"container-title":["Cellular &amp; Molecular Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41423-019-0353-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41423-019-0353-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41423-019-0353-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:22:49Z","timestamp":1684617769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41423-019-0353-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,3]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["353"],"URL":"https:\/\/doi.org\/10.1038\/s41423-019-0353-7","relation":{},"ISSN":["1672-7681","2042-0226"],"issn-type":[{"value":"1672-7681","type":"print"},{"value":"2042-0226","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,3]]},"assertion":[{"value":"10 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}