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dc.contributor.authorCarmona, G.
dc.contributor.authorPerera, U.
dc.contributor.authorGillett, C.
dc.contributor.authorNaba, A.
dc.contributor.authorLaw, Ah-Lai
dc.contributor.authorSharma, V.P.
dc.contributor.authorWang, J.
dc.contributor.authorWyckoff, J.
dc.contributor.authorBalsamo, M.
dc.contributor.authorMosis, F.
dc.contributor.authorDe Piano, M.
dc.contributor.authorMonypenny, J.
dc.contributor.authorWoodman, N.
dc.contributor.authorMcConnell, R.E
dc.contributor.authorMouneimne, G.
dc.contributor.authorVan Hemelrijck, M.
dc.contributor.authorCao, Y.
dc.contributor.authorCondeelis, J.
dc.contributor.authorHynes, R.O.
dc.contributor.authorGertler, F.B.
dc.contributor.authorKrause, Matthias
dc.contributor.illustrator
dc.date.accessioned2020-11-26T13:57:08Z
dc.date.available2016-03-21T00:00:00Z
dc.date.available2020-11-26T13:57:08Z
dc.date.issued2016-03-21
dc.identifier.citationCarmona G, Perera U, Gillett C, Naba A, Law AL, Sharma VP, Wang J, Wyckoff J, Balsamo M, Mosis F, De Piano M, Monypenny J, Woodman N, McConnell RE, Mouneimne G, Van Hemelrijck M, Cao Y., Condeelis J, Hynes RO, Gertler FB, Krause M (2016) 'Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE', Oncogene, 35 (39), pp.5155-5169.en_US
dc.identifier.issn0950-9232
dc.identifier.pmid26996666
dc.identifier.doi10.1038/onc.2016.47
dc.identifier.urihttp://hdl.handle.net/10547/624686
dc.description.abstractCancer invasion is a hallmark of metastasis. The mesenchymal mode of cancer cell invasion is mediated by elongated membrane protrusions driven by the assembly of branched F-actin networks. How deregulation of actin regulators promotes cancer cell invasion is still enigmatic. We report that increased expression and membrane localization of the actin regulator Lamellipodin correlate with reduced metastasis-free survival and poor prognosis in breast cancer patients. In agreement, we find that Lamellipodin depletion reduced lung metastasis in an orthotopic mouse breast cancer model. Invasive 3D cancer cell migration as well as invadopodia formation and matrix degradation was impaired upon Lamellipodin depletion. Mechanistically, we show that Lamellipodin promotes invasive 3D cancer cell migration via both actin-elongating Ena/VASP proteins and the Scar/WAVE complex, which stimulates actin branching. In contrast, Lamellipodin interaction with Scar/WAVE but not with Ena/VASP is required for random 2D cell migration. We identified a phosphorylation-dependent mechanism that regulates selective recruitment of these effectors to Lamellipodin: Abl-mediated Lamellipodin phosphorylation promotes its association with both Scar/WAVE and Ena/VASP, whereas Src-dependent phosphorylation enhances binding to Scar/WAVE but not to Ena/VASP. Through these selective, regulated interactions Lamellipodin mediates directional sensing of epidermal growth factor (EGF) gradients and invasive 3D migration of breast cancer cells. Our findings imply that increased Lamellipodin levels enhance Ena/VASP and Scar/WAVE activities at the plasma membrane to promote 3D invasion and metastasis.en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urlhttps://www.nature.com/articles/onc201647en_US
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031503/en_US
dc.rightsYellow - can archive pre-print (ie pre-refereeing)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectLamellipodinen_US
dc.subjectcancer cellsen_US
dc.subjectSubject Categories::C130 Cell Biologyen_US
dc.titleLamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVEen_US
dc.typeArticleen_US
dc.identifier.journalOncogeneen_US
dc.identifier.pmcidPMC5031503
dc.date.updated2020-11-26T13:47:47Z
dc.description.noteopen access


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