{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:33:59Z","timestamp":1791516839771,"version":"4.3.4"},"reference-count":179,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"DOI":"10.3389\/fcvm.2020.597374","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T04:32:45Z","timestamp":1605155565000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":45,"title":["Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics"],"prefix":"10.3389","volume":"7","author":[{"given":"Khoa","family":"Bui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Kwon","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2935","DOI":"10.1113\/jphysiol.2011.208298","article-title":"Lymphatic fluid: exchange mechanisms and regulation","volume":"589","author":"Huxley","year":"2011","journal-title":"J Physiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1093\/cvr\/cvq062","article-title":"Microvascular fluid exchange and the revised starling principle","volume":"87","author":"Levick","year":"2010","journal-title":"Cardiovasc Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1089\/lrb.2013.0012","article-title":"Lymphatic function and immune regulation in health and disease","volume":"11","author":"Liao","year":"2013","journal-title":"Lymphatic Res Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"E52","DOI":"10.1111\/j.1749-6632.2010.05716.x","article-title":"Mechanisms of chylomicron uptake into lacteals","volume":"1207","author":"Dixon","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nrc3677","article-title":"Lymphangiogenesis and lymphatic vessel remodelling in cancer","volume":"14","author":"Stacker","year":"2014","journal-title":"Nat Rev Cancer."},{"key":"B6","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.cell.2010.01.045","article-title":"Lymphangiogenesis: molecular mechanisms and future promise","volume":"140","author":"Tammela","year":"2010","journal-title":"Cell."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1093\/emboj\/21.7.1505","article-title":"An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype","volume":"21","author":"Wigle","year":"2002","journal-title":"EMBO J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nri1258","article-title":"Lymphatic vasculature development","volume":"4","author":"Oliver","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2726","DOI":"10.1158\/1078-0432.CCR-11-3237","article-title":"Molecular pathways: vasculogenic mimicry in tumor cells: diagnostic and therapeutic implications","volume":"18","author":"Kirschmann","year":"2012","journal-title":"Clin Cancer Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4274","DOI":"10.1073\/pnas.1016030108","article-title":"Transdifferentiation of glioblastoma cells into vascular endothelial cells","volume":"108","author":"Soda","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"6223","DOI":"10.1073\/pnas.1115542109","article-title":"In vivo imaging of lymphatic vessels in development, wound healing, inflammation, and tumor metastasis","volume":"109","author":"Mart\u00ednez-Corral","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1161\/CIRCULATIONAHA.115.020143","article-title":"Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction","volume":"133","author":"Henri","year":"2016","journal-title":"Circulation"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1101\/gad.16974811","article-title":"Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves","volume":"25","author":"Srinivasan","year":"2011","journal-title":"Genes Dev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/S0092-8674(00)81511-1","article-title":"Prox1 function is required for the development of the murine lymphatic system","volume":"98","author":"Wigle","year":"1999","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1038\/ng1642","article-title":"Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity","volume":"37","author":"Harvey","year":"2005","journal-title":"Nat Genet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ni1013","article-title":"Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins","volume":"5","author":"Karkkainen","year":"2004","journal-title":"Nat Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1126\/science.282.5390.946","article-title":"Cardiovascular failure in mouse embryos deficient in VEGF receptor-3","volume":"282","author":"Dumont","year":"1998","journal-title":"Science"},{"key":"B18","unstructured":"A model for gene therapy of human hereditary lymphedema1267782\n            KarkkainenMJ\n            SaaristoA\n            JussilaL\n            KarilaKA\n            LawrenceEC\n            PajusolaK\n          10.1073\/pnas.22144919811592985Proc Natl Acad Sci USA982001"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1182\/blood.V96.12.3793","article-title":"VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis","volume":"96","author":"Hamada","year":"2000","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1172\/JCI80465","article-title":"Foxc1 and Foxc2 deletion causes abnormal lymphangiogenesis and correlates with ERK hyperactivation","volume":"126","author":"Fatima","year":"2016","journal-title":"J Clin Invest"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1242\/dev.043489","article-title":"H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice","volume":"137","author":"Ichise","year":"2010","journal-title":"Development"},{"key":"B22","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1172\/JCI46116","article-title":"RASA1 maintains the lymphatic vasculature in a quiescent functional state in mice","volume":"122","author":"Lapinski","year":"2012","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.2353\/ajpath.2010.091301","article-title":"Akt\/protein kinase B is required for lymphatic network formation, remodeling, and valve development","volume":"177","author":"Zhou","year":"2010","journal-title":"Am J Pathol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4541","DOI":"10.1128\/MCB.01600-06","article-title":"Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling","volume":"27","author":"Taniguchi","year":"2007","journal-title":"Mol Cell Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1016\/j.celrep.2019.07.072","article-title":"VE-cadherin is required for lymphatic valve formation and maintenance","volume":"28","author":"Yang","year":"2019","journal-title":"Cell Rep"},{"key":"B26","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0092-8674(00)81010-7","article-title":"Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis","volume":"98","author":"Carmeliet","year":"1999","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1172\/JCI200522037","article-title":"Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation","volume":"115","author":"Baluk","year":"2005","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3389\/fimmu.2019.00308","article-title":"Inflammation and lymphatic function","volume":"10","author":"Schwager","year":"2019","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s00441-003-0748-7","article-title":"Lymphangiogenesis and tumor metastasis","volume":"314","author":"Pepper","year":"2003","journal-title":"Cell Tissue Res"},{"key":"B30","unstructured":"Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3199205\n            M\u00e4kinenT\n            JussilaL\n            VeikkolaT\n            KarpanenT\n            KettunenMI\n            PulkkanenKJ\n          10.1038\/8465111175851Nat Med72001"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1111\/j.1582-4934.2009.00834.x","article-title":"Lymphangiogenesis and cancer metastasis","volume":"13","author":"Mumprecht","year":"2009","journal-title":"J Cell Mol Med"},{"key":"B32","unstructured":"Vascular endothelial growth factor c promotes tumor lymphangiogenesis and intralymphatic tumor growth178690\n            KarpanenT\n            EgebladM\n            KarkkainenMJ\n            KuboH\n            Yl\u00e4-HerttualaS\n            J\u00e4\u00e4ttel\u00e4M\n          11280723Cancer Res612001"},{"key":"B33","doi-asserted-by":"publisher","first-page":"303","DOI":"10.21147\/j.issn.1000-9604.2017.04.03","article-title":"A review on Eph\/ephrin, angiogenesis and lymphangiogenesis in gastric, colorectal and pancreatic cancers","volume":"29","author":"Rudno-Rudzi\u0144ska","year":"2017","journal-title":"Chin J Cancer Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s10147-014-0684-4","article-title":"Update of molecular pathobiology in oral cancer: a review","volume":"19","author":"Sasahira","year":"2014","journal-title":"Int J Clin Oncol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"69ra11","DOI":"10.1126\/scitranslmed.3001699","article-title":"Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis","volume":"3","author":"Tammela","year":"2011","journal-title":"Sci Transl Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1172\/JCI71606","article-title":"Mechanisms of lymphatic metastasis","volume":"124","author":"Karaman","year":"2014","journal-title":"J Clin Invest"},{"key":"B37","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1159\/000454696","article-title":"Underlying mechanisms for distant metastasis - molecular biology","volume":"33","author":"Pachmayr","year":"2017","journal-title":"Visceral Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1172\/JCI79434","article-title":"Lymphatic vessels regulate immune microenvironments in human and murine melanoma","volume":"126","author":"Lund","year":"2016","journal-title":"J Clin Invest"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1084\/jem.20180654","article-title":"IFN\u03b3-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin","volume":"215","author":"Lane","year":"2018","journal-title":"J Exp Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nrc3186","article-title":"Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity","volume":"12","author":"Swartz","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1126\/science.1071420","article-title":"Lymphatic metastasis in the absence of functional intratumor lymphatics","volume":"296","author":"Padera","year":"2002","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/path.1942","article-title":"Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4\/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis","volume":"209","author":"Schledzewski","year":"2006","journal-title":"J Pathol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure - an obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"B44","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0925-4773(02)00240-X","article-title":"Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm","volume":"118","author":"Burke","year":"2002","journal-title":"Mech Dev"},{"key":"B45","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S0925-4773(01)00645-1","article-title":"Prox1 is differentially localized during lens development","volume":"112","author":"Duncan","year":"2002","journal-title":"Mech Dev"},{"key":"B46","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/dvdy.21024","article-title":"Prox1 expression patterns in the developing and adult murine brain","volume":"236","author":"Lavado","year":"2007","journal-title":"Dev Dyn"},{"key":"B47","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1242\/dev.030007","article-title":"Prox1 maintains muscle structure and growth in the developing heart","volume":"136","author":"Risebro","year":"2009","journal-title":"Development"},{"key":"B48","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.ccr.2008.02.020","article-title":"Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype","volume":"13","author":"Petrova","year":"2008","journal-title":"Cancer Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"3960","DOI":"10.1172\/JCI75392","article-title":"Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity","volume":"124","author":"Park","year":"2014","journal-title":"J Clin Invest"},{"key":"B50","doi-asserted-by":"publisher","first-page":"4912","DOI":"10.1172\/JCI120446","article-title":"Lymphatic mimicry in maternal endothelial cells promotes placental spiral artery remodeling","volume":"129","author":"Pawlak","year":"2019","journal-title":"J Clin Invest"},{"key":"B51","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fphys.2020.00114","article-title":"Lymphatic programing and specialization in hybrid vessels","volume":"11","author":"Pawlak","year":"2020","journal-title":"Front. Physiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.placenta.2005.12.006","article-title":"The uterine spiral arteries in human pregnancy: facts and controversies","volume":"27","author":"Pijnenborg","year":"2006","journal-title":"Placenta"},{"key":"B53","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/dvdy.10163","article-title":"Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate","volume":"225","author":"Hong","year":"2002","journal-title":"Dev Dyn"},{"key":"B54","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.1242\/jcs.052324","article-title":"Identification of targets of Prox1 during in vitro vascular differentiation from embryonic stem cells: functional roles of HoxD8 in lymphangiogenesis","volume":"122","author":"Harada","year":"2009","journal-title":"J Cell Sci"},{"key":"B55","doi-asserted-by":"publisher","first-page":"4593","DOI":"10.1093\/emboj\/cdf470","article-title":"Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor","volume":"21","author":"Petrova","year":"2002","journal-title":"EMBO J."},{"key":"B56","first-page":"163","article-title":"Threading analysis of prospero-type homeodomains","volume":"1","author":"Banerjee-Basu","year":"1999","journal-title":"In Silico Biol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1016\/S0969-2126(02)00883-3","article-title":"Structure of the DNA binding region of prospero reveals a novel homeo-prospero domain","volume":"10","author":"Ryter","year":"2002","journal-title":"Structure"},{"key":"B58","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.str.2005.01.023","article-title":"Structural basis of prospero-DNA interaction: implications for transcription regulation in developing cells","volume":"13","author":"Yousef","year":"2005","journal-title":"Structure"},{"key":"B59","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1091\/mbc.e05-04-0368","article-title":"Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis","volume":"17","author":"Shin","year":"2006","journal-title":"Mol Biol Cell"},{"key":"B60","doi-asserted-by":"publisher","first-page":"9531","DOI":"10.1038\/s41598-018-27739-w","article-title":"PROX1 is a transcriptional regulator of MMP14","volume":"8","author":"Gramolelli","year":"2018","journal-title":"Sci Rep"},{"key":"B61","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1007\/s10555-012-9390-8","article-title":"Transcription factor PROX1: its role in development and cancer","volume":"31","author":"Elsir","year":"2012","journal-title":"Cancer Metastasis Rev"},{"key":"B62","doi-asserted-by":"publisher","first-page":"e92534","DOI":"10.1371\/journal.pone.0092534","article-title":"Prox1 and FOXC2 act as regulators of lymphangiogenesis and angiogenesis in oral squamous cell carcinoma","volume":"9","author":"Sasahira","year":"2014","journal-title":"PLoS ONE"},{"key":"B63","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1210\/me.2004-0009","article-title":"Prospero-related homeobox (Prox1) is a corepressor of human liver receptor homolog-1 and suppresses the transcription of the cholesterol 7-\u03b1-hydroxylase gene","volume":"18","author":"Qin","year":"2004","journal-title":"Mol Endocrinol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/sj.embor.7400147","article-title":"Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue","volume":"5","author":"Steffensen","year":"2004","journal-title":"EMBO Rep"},{"key":"B65","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1101\/gad.1871610","article-title":"The homeobox protein Prox1 is a negative modulator of ERR{alpha}\/PGC-1{alpha} bioenergetic functions","volume":"24","author":"Charest-Marcotte","year":"2010","journal-title":"Genes Dev"},{"key":"B66","doi-asserted-by":"publisher","first-page":"10081","DOI":"10.1074\/jbc.M513420200","article-title":"A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene","volume":"281","author":"Song","year":"2006","journal-title":"J Biol Chem"},{"key":"B67","doi-asserted-by":"publisher","first-page":"6992","DOI":"10.1093\/nar\/gkt447","article-title":"Prospero-related homeobox 1 (Prox1) functions as a novel modulator of retinoic acid-related orphan receptors \u03b1- and \u03b3-mediated transactivation","volume":"41","author":"Takeda","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mam.2014.12.003","article-title":"Retinoic acid receptors: from molecular mechanisms to cancer therapy","volume":"41","author":"di Masi","year":"2015","journal-title":"Mol Aspects Med"},{"key":"B69","doi-asserted-by":"publisher","first-page":"24081","DOI":"10.1074\/jbc.M201821200","article-title":"CREB-binding protein\/p300 Co-activation of crystallin gene expression","volume":"277","author":"Chen","year":"2002","journal-title":"J Biol Chem"},{"key":"B70","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41467-017-00772-5","article-title":"An HDAC3-PROX1 corepressor module acts on HNF4\u03b1 to control hepatic triglycerides","volume":"8","author":"Armour","year":"2017","journal-title":"Nat Commun"},{"key":"B71","doi-asserted-by":"publisher","first-page":"e62192","DOI":"10.1371\/journal.pone.0062192","article-title":"Prox1 directly interacts with LSD1 and recruits the LSD1\/NuRD complex to epigenetically co-repress CYP7A1 transcription","volume":"8","author":"Ouyang","year":"2013","journal-title":"PLoS ONE"},{"key":"B72","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1158\/0008-5472.CAN-18-0451","article-title":"Transcription factor PROX1 suppresses notch pathway activation via the nucleosome remodeling and deacetylase complex in colorectal cancer stem-like cells","volume":"78","author":"H\u00f6gstr\u00f6m","year":"2018","journal-title":"Cancer Res"},{"key":"B73","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S1535-6108(02)00051-X","article-title":"Molecular mechanisms of lymphangiogenesis in health and disease","volume":"1","author":"Alitalo","year":"2002","journal-title":"Cancer Cell"},{"key":"B74","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1160\/TH03-04-0200","article-title":"Lymphangiogenic growth factors, receptors and therapies","volume":"90","author":"Lohela","year":"2003","journal-title":"Thromb Haemost"},{"key":"B75","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nrm1911","article-title":"VEGF receptor signalling? in control of vascular function","volume":"7","author":"Olsson","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"3566","DOI":"10.1073\/pnas.92.8.3566","article-title":"Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development","volume":"92","author":"Kaipainen","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"B77","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/sj.gt.3301723","article-title":"Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors","volume":"9","author":"Rafii","year":"2002","journal-title":"Gene Ther"},{"key":"B78","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/S0968-0004(03)00193-2","article-title":"VEGF-receptor signal transduction","volume":"28","author":"Cross","year":"2003","journal-title":"Trends Biochem Sci"},{"key":"B79","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1002\/j.1460-2075.1996.tb00359.x","article-title":"A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases","volume":"15","author":"Joukov","year":"1996","journal-title":"EMBO J"},{"key":"B80","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/gb-2005-6-2-209","article-title":"The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease","volume":"6","author":"Holmes","year":"2005","journal-title":"Genome Biol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1093\/jnci\/87.7.506","article-title":"Expression of vascular endothelial growt factor and its receptors fit and KDR in ovarian carcinoma","volume":"87","author":"Boocock","year":"1995","journal-title":"J Natl Cancer Inst"},{"key":"B82","doi-asserted-by":"publisher","first-page":"12607","DOI":"10.1074\/jbc.270.21.12607","article-title":"H\u00fcbner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of vascular endothelial growth factor expression in cultured keratinocytes.: implications for normal and impaired wound healing","volume":"270","author":"Frank","year":"1995","journal-title":"J Biol Chem"},{"key":"B83","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/jlb.55.3.410","article-title":"Macrophages and angiogenesis","volume":"55","author":"Sunderk\u00f6tter","year":"1994","journal-title":"J Leukoc Biol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jss.2008.04.023","article-title":"The role of vascular endothelial growth factor in wound healing","volume":"153","author":"Bao","year":"2009","journal-title":"J Res"},{"key":"B85","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat Med"},{"key":"B86","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/9467","article-title":"VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation","volume":"5","author":"Gerber","year":"1999","journal-title":"Nat Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.jacbts.2017.02.005","article-title":"Cardiac lymphatic vessels, transport, and healing of the infarcted heart","volume":"2","author":"Huang","year":"2017","journal-title":"Basic Transl Sci"},{"key":"B88","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/j.1365-2559.2007.02785.x","article-title":"Lymphangiogenesis in myocardial remodelling after infarction","volume":"51","author":"Ishikawa","year":"2007","journal-title":"Histopathology"},{"key":"B89","doi-asserted-by":"publisher","first-page":"3402","DOI":"10.1172\/JCI97192","article-title":"The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction","volume":"128","author":"Vieira","year":"2018","journal-title":"J Clin Invest"},{"key":"B90","doi-asserted-by":"publisher","first-page":"5598","DOI":"10.1038\/sj.onc.1203855","article-title":"Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis","volume":"19","author":"Karkkainen","year":"2000","journal-title":"Oncogene"},{"key":"B91","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/sj.bjc.6603487","article-title":"The role of the VEGF-C\/VEGFR-3 axis in cancer progression","volume":"96","author":"Su","year":"2007","journal-title":"Br J Cancer"},{"key":"B92","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1097\/00006676-200104000-00010","article-title":"Overexpression of lymphangiogenic growth factor VEGF-C in human pancreatic cancer","volume":"22","author":"Tang","year":"2001","journal-title":"Pancreas"},{"key":"B93","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1477-7819-3-2","article-title":"Expression of vascular endothelial growth factor (VEGF)-C in preoperative biopsy specimens and metastatic foci of regional lymph nodes in submucosal gastric carcinoma","volume":"3","author":"Ishikawa","year":"2005","journal-title":"World J Surg Oncol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1002\/ijc.10283","article-title":"VEGF-C induced lymphangiogenesis is associated with lymph node metastasis in orthotopic MCF-7 tumors","volume":"98","author":"Mattila","year":"2002","journal-title":"Int J Cancer"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1126\/science.286.5445.1741","article-title":"Phosphorylation and regulation of raf by akt (protein kinase B)","volume":"286","author":"Zimmermann","year":"1999","journal-title":"Science"},{"key":"B96","doi-asserted-by":"publisher","first-page":"27168","DOI":"10.1074\/jbc.274.38.27168","article-title":"90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1","volume":"274","author":"Jensen","year":"1999","journal-title":"J Biol Chem"},{"key":"B97","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1177\/1947601911411084","article-title":"Ras in cancer and developmental diseases","volume":"2","author":"Fern\u00e1ndez-Medarde","year":"2011","journal-title":"Genes Cancer"},{"key":"B98","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1056\/NEJMoa032691","article-title":"Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer","volume":"350","author":"Hurwitz","year":"2004","journal-title":"N Engl J Med"},{"key":"B99","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00280-016-3134-3","article-title":"Phase 1 study of the anti-vascular endothelial growth factor receptor 3 monoclonal antibody LY3022856\/IMC-3C5 in patients with advanced and refractory solid tumors and advanced colorectal cancer","volume":"78","author":"Saif","year":"2016","journal-title":"Cancer Chemother Pharmacol"},{"key":"B100","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.1200\/jco.2014.32.15_suppl.2524","article-title":"A first-in-human phase I study of VGX-100, a selective anti-VEGF-C antibody, alone and in combination with bevacizumab in patients with advanced solid tumors","volume":"32","author":"Falchook","year":"2014","journal-title":"J Clin Oncol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"49289","DOI":"10.1074\/jbc.M108069200","article-title":"Vascular endothelial growth factor induction of the angiogenic phenotype requires ras activation","volume":"276","author":"Meadows","year":"2001","journal-title":"J Biol Chem"},{"key":"B102","doi-asserted-by":"publisher","first-page":"4762","DOI":"10.1093\/emboj\/20.17.4762","article-title":"Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C\/D receptor VEGFR-3","volume":"20","author":"M\u00e4kinen","year":"2001","journal-title":"EMBO J"},{"key":"B103","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1161\/ATVBAHA.114.304881","article-title":"Molecular controls of lymphatic VEGFR3 signaling","volume":"35","author":"Deng","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B104","doi-asserted-by":"publisher","first-page":"31099","DOI":"10.1074\/jbc.M111974200","article-title":"Regulation of Raf-Akt cross-talk","volume":"277","author":"Moelling","year":"2002","journal-title":"J Biol Chem"},{"key":"B105","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1177\/1947601911408081","article-title":"Functional specificity of ras isoforms: so similar but so different","volume":"2","author":"Castellano","year":"2011","journal-title":"Genes Cancer."},{"key":"B106","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1146\/annurev-genom-091212-153523","article-title":"The RASopathies","volume":"14","author":"Rauen","year":"2013","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"B107","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1210\/er.2017-00232","article-title":"The RASopathy family: consequences of germline activation of the RAS\/MAPK pathway","volume":"39","author":"Tajan","year":"2018","journal-title":"Endocr Rev"},{"key":"B108","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/ejhg.2015.175","article-title":"The lymphatic phenotype in noonan and cardiofaciocutaneous syndrome","volume":"24","author":"Joyce","year":"2016","journal-title":"Eur J Hum Genet"},{"key":"B109","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1159\/000343355","article-title":"Ras activated ERK and PI3K pathways differentially affect directional movement of cultured fibroblasts","volume":"31","author":"Sepe","year":"2013","journal-title":"Cell Physiol Biochem."},{"key":"B110","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.tcm.2013.09.004","article-title":"Lymphatic vessel abnormalities arising from disorders of ras signal transduction","volume":"24","author":"Sevick-Muraca","year":"2014","journal-title":"Trends Cardiovasc Med"},{"key":"B111","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/pd.2666","article-title":"Aberrant lymphatic development in euploid fetuses with increased nuchal translucency including Noonan syndrome","volume":"31","author":"de Mooij","year":"2011","journal-title":"Prenatal Diagn"},{"key":"B112","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/ng1748","article-title":"Germline KRAS mutations cause noonan syndrome","volume":"38","author":"Schubbert","year":"2006","journal-title":"Nat Genet"},{"key":"B113","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.apsb.2019.03.002","article-title":"Targeting the untargetable KRAS in cancer therapy","volume":"9","author":"Liu","year":"2019","journal-title":"Acta Pharma Sin B"},{"key":"B114","doi-asserted-by":"publisher","first-page":"re1","DOI":"10.1126\/scisignal.2003669","article-title":"Nonredundant functions for Ras GTPase-activating proteins in tissue homeostasis","volume":"6","author":"King","year":"2013","journal-title":"Sci Signal"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1242\/jcs.182873","article-title":"RAS isoforms and mutations in cancer at a glance","volume":"129","author":"Hobbs","year":"2016","journal-title":"J Cell Sci"},{"key":"B116","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1038\/ng2113","article-title":"Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype","volume":"39","author":"Brems","year":"2007","journal-title":"Nat Genet"},{"key":"B117","doi-asserted-by":"publisher","first-page":"e49222","DOI":"10.1371\/journal.pone.0049222","article-title":"Loss of NF1 expression in human endothelial cells promotes autonomous proliferation and altered vascular morphogenesis","volume":"7","author":"Bajaj","year":"2012","journal-title":"PLoS ONE"},{"key":"B118","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1101\/gad.190876.112","article-title":"A shared molecular mechanism underlies the human rasopathies Legius syndrome and neurofibromatosis-1","volume":"26","author":"Stowe","year":"2012","journal-title":"Genes Dev"},{"key":"B119","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1128\/MCB.00191-16","article-title":"SPRED1 Interferes with K-ras but Not H-ras membrane anchorage and signaling","volume":"36","author":"Siljam\u00e4ki","year":"2016","journal-title":"Mol Cell Biol"},{"key":"B120","doi-asserted-by":"publisher","first-page":"9508","DOI":"10.1074\/jbc.M112.367763","article-title":"MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1)","volume":"288","author":"Sun","year":"2013","journal-title":"J Biol Chem"},{"key":"B121","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s41065-018-0062-8","article-title":"A novel RASA1 mutation causing capillary malformation-arteriovenous malformation (CM-AVM): the first genetic clinical report in East Asia","volume":"155","author":"Cai","year":"2018","journal-title":"Hereditas"},{"key":"B122","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1002\/ajmg.a.37613","article-title":"RASA1 somatic mutation and variable expressivity in capillary malformation\/arteriovenous malformation (CM\/AVM) syndrome","volume":"170","author":"Macmurdo","year":"2016","journal-title":"Am J Med Genet A"},{"key":"B123","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1172\/JCI89607","article-title":"RASA1 regulates the function of lymphatic vessel valves in mice","volume":"127","author":"Lapinski","year":"2017","journal-title":"J Clin Invest"},{"key":"B124","doi-asserted-by":"publisher","first-page":"3545","DOI":"10.1172\/JCI124917","article-title":"RASA1-dependent cellular export of collagen IV controls blood and lymphatic vascular development","volume":"129","author":"Chen","year":"2019","journal-title":"J Clin Invest"},{"key":"B125","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1177\/1947601911408079","article-title":"RAS interaction with PI3K: more than just another effector pathway","volume":"2","author":"Castellano","year":"2011","journal-title":"Genes Cancer"},{"key":"B126","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3389\/fonc.2014.00252","article-title":"The PTEN\/PI3K\/AKT pathway in vivo, cancer mouse models","volume":"4","author":"Carnero","year":"2014","journal-title":"Front Oncol"},{"key":"B127","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0065-230X(09)02002-8","article-title":"PI3K\/PTEN signaling in angiogenesis and tumorigenesis","volume":"102","author":"Jiang","year":"2009","journal-title":"Adv Cancer Res"},{"key":"B128","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S0960-9822(06)00122-9","article-title":"Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B\u03b1","volume":"7","author":"Alessi","year":"1997","journal-title":"Curr Biol"},{"key":"B129","doi-asserted-by":"publisher","first-page":"a011189","DOI":"10.1101\/cshperspect.a011189","article-title":"PI3K-PKB\/Akt pathway","volume":"4","author":"Hemmings","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B130","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nat Cell Biol"},{"key":"B131","doi-asserted-by":"publisher","first-page":"15020","DOI":"10.1073\/pnas.011318098","article-title":"PDK1 regulates growth through Akt and S6K in Drosophila","volume":"98","author":"Rintelen","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B132","doi-asserted-by":"publisher","first-page":"5416","DOI":"10.1038\/ncomms6416","article-title":"The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon regeneration","volume":"5","author":"Yang","year":"2014","journal-title":"Nat Commun"},{"key":"B133","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K pathway in human disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"B134","doi-asserted-by":"publisher","first-page":"e28947","DOI":"10.1371\/journal.pone.0028947","article-title":"Phosphorylation of Akt and ERK1\/2 is required for VEGF-A\/VEGFR2-induced proliferation and migration of lymphatic endothelium","volume":"6","author":"Dellinger","year":"2011","journal-title":"PLoS ONE"},{"key":"B135","unstructured":"9-cis retinoic acid promotes lymphangiogenesis and enhances lymphatic vessel regeneration: therapeutic implications of 9-cis retinoic acid for secondary lymphedema87282\n            ChoiI\n            LeeS\n            Kyoung ChungH\n            Suk LeeY\n            Eui KimK\n            ChoiD\n          10.1161\/CIRCULATIONAHA.111.03029622275501Circulation1252012"},{"key":"B136","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1002\/dvdy.22078","article-title":"Organ-specific lymphangiectasia, arrested lymphatic sprouting, and maturation defects resulting from gene-targeting of the PI3K regulatory isoforms p85\u03b1, p55\u03b1, and p50\u03b1","volume":"238","author":"Mouta-Bellum","year":"2009","journal-title":"Dev Dyn"},{"key":"B137","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s10456-020-09722-0","article-title":"Constitutively active PIK3CA mutations are expressed by lymphatic and vascular endothelial cells in capillary lymphatic venous malformation","volume":"23","author":"Le Cras","year":"2020","journal-title":"Angiogenesis"},{"key":"B138","doi-asserted-by":"publisher","first-page":"15259","DOI":"10.1073\/pnas.1205508109","article-title":"Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110\u03b1 (andlt;emandgt;PIK3CAandlt;\/emandgt;)","volume":"109","author":"Burke","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B139","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.tibs.2014.12.003","article-title":"Synergy in activating class I PI3Ks","volume":"40","author":"Burke","year":"2015","journal-title":"Trends Biochem Sci"},{"key":"B140","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.jpeds.2014.12.069","article-title":"Lymphatic and other vascular malformative\/overgrowth disorders are caused by somatic mutations in PIK3CA","volume":"166","author":"Luks","year":"2015","journal-title":"J Pediatr"},{"key":"B141","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1038\/s41467-020-16496-y","article-title":"Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation","volume":"11","author":"Martinez-Corral","year":"2020","journal-title":"Nat Commun"},{"key":"B142","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/1235","article-title":"Pten is essential for embryonic development and tumour suppression","volume":"19","author":"Cristofano","year":"1998","journal-title":"Nat Genet"},{"key":"B143","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1016\/S0960-9822(07)00488-5","article-title":"High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice","volume":"8","author":"Suzuki","year":"1998","journal-title":"Curr Biol"},{"key":"B144","doi-asserted-by":"publisher","first-page":"e39558","DOI":"10.1371\/journal.pone.0039558","article-title":"Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis","volume":"7","author":"Coso","year":"2012","journal-title":"PLoS ONE"},{"key":"B145","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1158\/1078-0432.CCR-10-0434","article-title":"Insulin receptor substrate regulation of phosphoinositide 3-kinase","volume":"17","author":"Metz","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B146","doi-asserted-by":"publisher","first-page":"5778","DOI":"10.1167\/iovs.10-6816","article-title":"Blockade of insulin receptor substrate-1 inhibits corneal lymphangiogenesis","volume":"52","author":"Hos","year":"2011","journal-title":"Investigat Ophthalmol Vis Sci"},{"key":"B147","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1083\/jcb.200507119","article-title":"Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning","volume":"173","author":"Cai","year":"2006","journal-title":"J Cell Biol"},{"key":"B148","doi-asserted-by":"publisher","first-page":"5644","DOI":"10.1128\/MCB.21.16.5644-5657.2001","article-title":"Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and proliferation of endothelial cells","volume":"21","author":"R\u00f6ssig","year":"2001","journal-title":"Mol Cell Biol"},{"key":"B149","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1002\/humu.20748","article-title":"The RAS\/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders","volume":"29","author":"Aoki","year":"2008","journal-title":"Hum Mut"},{"key":"B150","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.gde.2009.04.001","article-title":"The RASopathies: developmental syndromes of Ras\/MAPK pathway dysregulation","volume":"19","author":"Tidyman","year":"2009","journal-title":"Curr Opin Genet Dev"},{"key":"B151","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/ng2073","article-title":"Gain-of-function RAF1 mutations cause noonan and LEOPARD syndromes with hypertrophic cardiomyopathy","volume":"39","author":"Pandit","year":"2007","journal-title":"Nat Genet"},{"key":"B152","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/ng2078","article-title":"Germline gain-of-function mutations in RAF1 cause noonan syndrome","volume":"39","author":"Razzaque","year":"2007","journal-title":"Nat Genet"},{"key":"B153","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1242\/dev.137901","article-title":"Vegfc acts through ERK to induce sprouting and differentiation of trunk lymphatic progenitors","volume":"143","author":"Shin","year":"2016","journal-title":"Development"},{"key":"B154","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1172\/JCI63034","article-title":"Endothelial ERK signaling controls lymphatic fate specification","volume":"123","author":"Deng","year":"2013","journal-title":"J Clin Invest"},{"key":"B155","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/s41591-019-0479-2","article-title":"ARAF recurrent mutation causes central conducting lymphatic anomaly treatable with a MEK inhibitor","volume":"25","author":"Li","year":"2019","journal-title":"Nat Med"},{"key":"B156","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1038\/sj.leu.2402945","article-title":"Signal transduction mediated by the Ras\/Raf\/MEK\/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention","volume":"17","author":"Chang","year":"2003","journal-title":"Leukemia"},{"key":"B157","doi-asserted-by":"publisher","first-page":"32670","DOI":"10.1074\/jbc.M102776200","article-title":"Cross-talk between the ERK and p70 S6 Kinase (S6K) signaling pathways: MEK-dependent activation of S6K2 in cardiomyocytes","volume":"276","author":"Wang","year":"2001","journal-title":"J Biol Chem"},{"key":"B158","doi-asserted-by":"publisher","first-page":"7650","DOI":"10.1158\/0008-5472.CAN-08-1137","article-title":"Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation","volume":"68","author":"Zheng","year":"2008","journal-title":"Cancer Res"},{"key":"B159","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1042\/BJ20080281","article-title":"The TSC1-TSC2 complex: a molecular switchboard controlling cell growth","volume":"412","author":"Huang","year":"2008","journal-title":"Biochem J"},{"key":"B160","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.1101\/gad.1727208","article-title":"Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity","volume":"22","author":"Johnson","year":"2008","journal-title":"Genes Dev"},{"key":"B161","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1101\/gad.1859310","article-title":"The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells","volume":"24","author":"Srinivasan","year":"2010","journal-title":"Genes Dev"},{"key":"B162","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1182\/blood-2008-03-145789","article-title":"Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate","volume":"113","author":"Lee","year":"2009","journal-title":"Blood"},{"key":"B163","doi-asserted-by":"publisher","first-page":"49358","DOI":"10.1074\/jbc.M308071200","article-title":"CD13\/APN transcription is induced by RAS\/MAPK-mediated phosphorylation of Ets-2 in activated endothelial cells","volume":"278","author":"Petrovic","year":"2003","journal-title":"J Biol Chem"},{"key":"B164","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1242\/jcs.083998","article-title":"Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1","volume":"124","author":"Yoshimatsu","year":"2011","journal-title":"J Cell Sci"},{"key":"B165","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1101\/gad.216226.113","article-title":"The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors","volume":"28","author":"Srinivasan","year":"2014","journal-title":"Genes Dev"},{"key":"B166","doi-asserted-by":"publisher","first-page":"e51639","DOI":"10.1371\/journal.pone.0051639","article-title":"Ras\/MAPK signaling modulates VEGFR-3 expression through Ets-mediated p300 recruitment and histone acetylation on the Vegfr3 gene in lymphatic endothelial cells","volume":"7","author":"Ichise","year":"2012","journal-title":"PLoS ONE"},{"key":"B167","doi-asserted-by":"publisher","first-page":"4901","DOI":"10.1038\/onc.2011.187","article-title":"C\/EBP-\u03b4 regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1\u03b1","volume":"30","author":"Min","year":"2011","journal-title":"Oncogene"},{"key":"B168","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/nrd2380","article-title":"Molecular basis for sunitinib efficacy and future clinical development","volume":"6","author":"Faivre","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"B169","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3109\/08977199209023937","article-title":"The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies","volume":"7","author":"Kim","year":"1992","journal-title":"Growth Factors"},{"key":"B170","doi-asserted-by":"publisher","first-page":"117","DOI":"10.4103\/jrms.JRMS_182_17","article-title":"Acquired tumor resistance to antiangiogenic therapy: mechanisms at a glance","volume":"22","author":"Zarrin","year":"2017","journal-title":"J Res Med Sci"},{"key":"B171","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/S0140-6736(15)60898-4","article-title":"Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial","volume":"386","author":"Long","year":"2015","journal-title":"Lancet"},{"key":"B172","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S0140-6736(08)61039-9","article-title":"Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial","volume":"372","author":"Motzer","year":"2008","journal-title":"Lancet"},{"key":"B173","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.1002\/med.21496","article-title":"Potential lymphangiogenesis therapies: learning from current antiangiogenesis therapies-A review","volume":"38","author":"Yamakawa","year":"2018","journal-title":"Med Res Rev"},{"key":"B174","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/bies.20198","article-title":"Post-translational modifications influence transcription factor activity: a view from the ETS superfamily","volume":"27","author":"Tootle","year":"2005","journal-title":"BioEssays"},{"key":"B175","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.tips.2013.11.005","article-title":"Regulation of transcription factor activity by interconnected post-translational modifications","volume":"35","author":"Filtz","year":"2014","journal-title":"Trends Pharmacol Sci"},{"key":"B176","doi-asserted-by":"publisher","first-page":"3723","DOI":"10.1016\/j.febslet.2008.09.057","article-title":"Modulation of transcriptional corepressor activity of prospero-related homeobox protein (Prox1) by SUMO modification","volume":"582","author":"Shan","year":"2008","journal-title":"FEBS Lett"},{"key":"B177","doi-asserted-by":"publisher","first-page":"3358","DOI":"10.1242\/jcs.050005","article-title":"Sumoylation of Prox1 controls its ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells","volume":"122","author":"Pan","year":"2009","journal-title":"J Cell Sci"},{"key":"B178","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nature18003","article-title":"Proteogenomics connects somatic mutations to signalling in breast cancer","volume":"534","author":"Mertins","year":"2016","journal-title":"Nature"},{"key":"B179","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.cmet.2016.10.004","article-title":"Phosphorylation is a central mechanism for circadian control of metabolism and physiology","volume":"25","author":"Robles","year":"2017","journal-title":"Cell Metab"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2020.597374\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T04:32:51Z","timestamp":1605155571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2020.597374\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,12]]},"references-count":179,"alternative-id":["10.3389\/fcvm.2020.597374"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2020.597374","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,12]]},"article-number":"597374"}}