{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:05:15Z","timestamp":1790226315608,"version":"4.1.0"},"reference-count":207,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01HL111130"],"award-info":[{"award-number":["R01HL111130"]}]},{"name":"National Institutes of Health","award":["R01CA278599"],"award-info":[{"award-number":["R01CA278599"]}]},{"name":"National Institutes of Health","award":["R21AR081076"],"award-info":[{"award-number":["R21AR081076"]}]},{"name":"National Institutes of Health","award":["R21AG076132"],"award-info":[{"award-number":["R21AG076132"]}]},{"name":"National Institutes of Health","award":["T32CA009501"],"award-info":[{"award-number":["T32CA009501"]}]},{"name":"National Institutes of Health","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]},{"name":"Cancer Center","award":["R01HL111130"],"award-info":[{"award-number":["R01HL111130"]}]},{"name":"Cancer Center","award":["R01CA278599"],"award-info":[{"award-number":["R01CA278599"]}]},{"name":"Cancer Center","award":["R21AR081076"],"award-info":[{"award-number":["R21AR081076"]}]},{"name":"Cancer Center","award":["R21AG076132"],"award-info":[{"award-number":["R21AG076132"]}]},{"name":"Cancer Center","award":["T32CA009501"],"award-info":[{"award-number":["T32CA009501"]}]},{"name":"Cancer Center","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), a receptor tyrosine kinase encoded by the FLT4 gene, plays a significant role in the morphogenesis and maintenance of lymphatic vessels. Under both normal and pathologic conditions, VEGF-C and VEGF-D bind VEGFR3 on the surface of lymphatic endothelial cells (LECs) and induce lymphatic proliferation, migration, and survival by activating intracellular PI3K-Akt and MAPK-ERK signaling pathways. Impaired lymphatic function and VEGFR3 signaling has been linked with a myriad of commonly encountered clinical conditions. This review provides a brief overview of intracellular VEGFR3 signaling in LECs and explores examples of dysregulated VEGFR3 signaling in various disease states, including (1) lymphedema, (2) tumor growth and metastasis, (3) obesity and metabolic syndrome, (4) organ transplant rejection, and (5) autoimmune disorders. A more complete understanding of the molecular mechanisms underlying the lymphatic pathology of each disease will allow for the development of novel strategies to treat these chronic and often debilitating illnesses.<\/jats:p>","DOI":"10.3390\/cells13010068","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T11:44:57Z","timestamp":1703763897000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Dysregulation of Lymphatic Endothelial VEGFR3 Signaling in Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5087-5505","authenticated-orcid":false,"given":"Kevin","family":"Kuonqui","sequence":"first","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-9859","authenticated-orcid":false,"given":"Adana-Christine","family":"Campbell","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananta","family":"Sarker","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arielle","family":"Roberts","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bracha L.","family":"Pollack","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeung Ju","family":"Park","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyeon","family":"Shin","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stav","family":"Brown","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5717-697X","authenticated-orcid":false,"given":"Babak J.","family":"Mehrara","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghu P.","family":"Kataru","sequence":"additional","affiliation":[{"name":"Plastic and Reconstructive Surgery Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaax4063","DOI":"10.1126\/science.aax4063","article-title":"Biological functions of lymphatic vessels","volume":"369","author":"Petrova","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.devcel.2018.03.021","article-title":"Emerging Concepts in Organ-Specific Lymphatic Vessels and Metabolic Regulation of Lymphatic Development","volume":"45","author":"Wong","year":"2018","journal-title":"Dev. 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