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  • 1
    Abstract: Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of 〉 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells.
    Type of Publication: Journal article published
    PubMed ID: 25678558
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  • 2
    Publication Date: 2013-06-01
    Description: Local extinctions have cascading effects on ecosystem functions, yet little is known about the potential for the rapid evolutionary change of species in human-modified scenarios. We show that the functional extinction of large-gape seed dispersers in the Brazilian Atlantic forest is associated with the consistent reduction of the seed size of a keystone palm species. Among 22 palm populations, areas deprived of large avian frugivores for several decades present smaller seeds than nondefaunated forests, with negative consequences for palm regeneration. Coalescence and phenotypic selection models indicate that seed size reduction most likely occurred within the past 100 years, associated with human-driven fragmentation. The fast-paced defaunation of large vertebrates is most likely causing unprecedented changes in the evolutionary trajectories and community composition of tropical forests.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galetti, Mauro -- Guevara, Roger -- Cortes, Marina C -- Fadini, Rodrigo -- Von Matter, Sandro -- Leite, Abraao B -- Labecca, Fabio -- Ribeiro, Thiago -- Carvalho, Carolina S -- Collevatti, Rosane G -- Pires, Mathias M -- Guimaraes, Paulo R Jr -- Brancalion, Pedro H -- Ribeiro, Milton C -- Jordano, Pedro -- New York, N.Y. -- Science. 2013 May 31;340(6136):1086-90. doi: 10.1126/science.1233774.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Ecologia, Universidade Estadual Paulista, Rio Claro, Sao Paulo, Brazil.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Arecaceae ; *Biological Evolution ; *Birds ; Brazil ; *Extinction, Biological ; *Feeding Behavior ; *Germination ; Seeds/*anatomy & histology/physiology ; Trees
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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