Dysregulation of lymphatic endothelial VEGFR3 signaling in disease Review
| Authors: | Kuonqui, K.; Campbell, A. C.; Sarker, A.; Roberts, A.; Pollack, B. L.; Park, H. J.; Shin, J.; Brown, S.; Mehrara, B. J.; Kataru, R. P. |
| Review Title: | Dysregulation of lymphatic endothelial VEGFR3 signaling in disease |
| Abstract: | 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. © 2023 by the authors. |
| Keywords: | signal transduction; vasculotropin receptor 3; vascular endothelial growth factor a; unclassified drug; review; cancer growth; metastasis; inflammation; obesity; protein tyrosine kinase; phosphatidylinositol 3 kinase; endothelium cell; lymph vessel endothelium; lymphangiogenesis; lymphedema; endothelial cells; graft failure; vasculotropin a; triacylglycerol; metabolic syndrome x; graft rejection; autoimmune disease; chemokine receptor ccr7; peroxisome proliferator activated receptor gamma; angiopoietin 2; tumor necrosis factor; lymphatic system disease; mammalian target of rapamycin complex 1; neuropilin 2; phosphatidylinositol 3-kinases; lymphatics; endothelium, lymphatic; phosphatidylinositol; pi3k/akt signaling; semaphorin; lymphatic endothelial cell; phosphatidylinositol 4,5 bisphosphate 3 kinase catalytic subunit alpha; cancer; human; malignant neoplasm; rtk signaling; vegfr-3; semaphorin 3f; transcription factor foxc2 |
| Journal Title: | Cells |
| Volume: | 13 |
| Issue: | 1 |
| ISSN: | 2073-4409 |
| Publisher: | MDPI |
| Date Published: | 2024-01-01 |
| Start Page: | 68 |
| Language: | English |
| DOI: | 10.3390/cells13010068 |
| PUBMED: | 38201272 |
| PROVIDER: | scopus |
| PMCID: | PMC10778007 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Corresponding authors are MSK author: Babak J. Mehrara and Raghu P. Kataru -- Source: Scopus |
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