Show simple item record

dc.contributor.authorBachelder, Robin E.
dc.contributor.authorLipscomb, Elizabeth A.
dc.contributor.authorLin, Xuena
dc.contributor.authorWendt, Melissa A.
dc.contributor.authorChadborn, Neil H.
dc.contributor.authorEickholt, Britta J.
dc.contributor.authorMercurio, Arthur M.
dc.date2022-08-11T08:08:02.000
dc.date.accessioned2022-08-23T15:39:47Z
dc.date.available2022-08-23T15:39:47Z
dc.date.issued2003-09-23
dc.date.submitted2010-11-07
dc.identifier.citationCancer Res. 2003 Sep 1;63(17):5230-3.
dc.identifier.issn0008-5472 (Linking)
dc.identifier.pmid14500350
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26251
dc.description.abstractNeuropilin-1 (NP1), in conjunction with plexins, promotes axon repulsion by binding to semaphorin 3A (SEMA3A). Although NP1 is expressed in carcinoma cells, its functions have remained elusive, and neither SEMA3A nor plexin expression has been explored in cancer. Here we provide evidence that breast carcinoma cells support an autocrine pathway involving SEMA3A, plexin-A1, and NP1 that impedes their ability to chemotax. Reducing SEMA3A or NP1 expression by RNA interference or inhibiting plexin-A1 signaling enhanced migration. Conversely, expression of constitutively active plexin-A1 impaired chemotaxis. The paradox of how breast carcinoma cells expressing these endogenous chemotaxis inhibitors are able to migrate is explained by their expression of vascular endothelial growth factor (VEGF), a NP1 ligand that competes with SEMA3A for receptor binding. Finally, we establish that the ratio of endogenous VEGF and SEMA3A concentrations in carcinoma cells determines their chemotactic rate. Our findings lead to the surprising conclusion that opposing autocrine loops involving NP1 regulate the chemotaxis of breast carcinoma cells. Moreover, our data indicate a novel autocrine function for VEGF in chemotaxis.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=14500350&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://cancerres.aacrjournals.org/content/63/17/5230.full.pdf+html
dc.subjectBreast Neoplasms
dc.subjectCarcinoma
dc.subjectChemotaxis
dc.subjectEndothelial Growth Factors
dc.subjectHumans
dc.subjectIntercellular Signaling Peptides and Proteins
dc.subjectLigands
dc.subjectLymphokines
dc.subjectNerve Tissue Proteins
dc.subjectNeuropilin-1
dc.subjectRNA Interference
dc.subjectRNA, Messenger
dc.subjectReceptors, Cell Surface
dc.subjectSemaphorin-3A
dc.subjectTransfection
dc.subjectVascular Endothelial Growth Factor A
dc.subjectVascular Endothelial Growth Factors
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleCompeting autocrine pathways involving alternative neuropilin-1 ligands regulate chemotaxis of carcinoma cells
dc.typeJournal Article
dc.source.journaltitleCancer research
dc.source.volume63
dc.source.issue17
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/165
dc.identifier.contextkey1633390
html.description.abstract<p>Neuropilin-1 (NP1), in conjunction with plexins, promotes axon repulsion by binding to semaphorin 3A (SEMA3A). Although NP1 is expressed in carcinoma cells, its functions have remained elusive, and neither SEMA3A nor plexin expression has been explored in cancer. Here we provide evidence that breast carcinoma cells support an autocrine pathway involving SEMA3A, plexin-A1, and NP1 that impedes their ability to chemotax. Reducing SEMA3A or NP1 expression by RNA interference or inhibiting plexin-A1 signaling enhanced migration. Conversely, expression of constitutively active plexin-A1 impaired chemotaxis. The paradox of how breast carcinoma cells expressing these endogenous chemotaxis inhibitors are able to migrate is explained by their expression of vascular endothelial growth factor (VEGF), a NP1 ligand that competes with SEMA3A for receptor binding. Finally, we establish that the ratio of endogenous VEGF and SEMA3A concentrations in carcinoma cells determines their chemotactic rate. Our findings lead to the surprising conclusion that opposing autocrine loops involving NP1 regulate the chemotaxis of breast carcinoma cells. Moreover, our data indicate a novel autocrine function for VEGF in chemotaxis.</p>
dc.identifier.submissionpathcancerbiology_pp/165
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages5230-3


This item appears in the following Collection(s)

Show simple item record