A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
alpha 5 beta 1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3
Tekijät: Paul NR, Allen JL, Chapman A, Morlan-Mairal M, Zindy E, Jacquemet G, del Ama LF, Ferizovic N, Green DM, Howe JD, Ehler E, Hurlstone A, Caswell PT
Kustantaja: ROCKEFELLER UNIV PRESS
Julkaisuvuosi: 2015
Journal: Journal of Cell Biology
Tietokannassa oleva lehden nimi: JOURNAL OF CELL BIOLOGY
Lehden akronyymi: J CELL BIOL
Vuosikerta: 210
Numero: 6
Aloitussivu: 1013
Lopetussivu: 1031
Sivujen määrä: 19
ISSN: 0021-9525
eISSN: 1540-8140
DOI: https://doi.org/10.1083/jcb.201502040
Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of alpha 5 beta 1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP-alpha 5 beta 1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
