@article{4250e9ad7bc14741931998c84d8cb530,
title = "Mesenchymal Cell Invasion Requires Cooperative Regulation of Persistent Microtubule Growth by SLAIN2 and CLASP1",
abstract = "Microtubules regulate signaling, trafficking, and cell mechanics, but the respective contribution of these functions to cell morphogenesis and migration in 3D matrices is unclear. Here, we report that the microtubule plus-end tracking protein (+TIP) SLAIN2, which suppresses catastrophes, is not required for 2D cell migration but is essential for mesenchymal cell invasion in 3D culture and in a mouse cancer model. We show that SLAIN2 inactivation does not affect Rho GTPase activity, trafficking, and focal adhesion formation. However, SLAIN2-dependent catastrophe inhibition determines microtubule resistance to compression and pseudopod elongation. Another +TIP, CLASP1, is also needed to form invasive pseudopods because it prevents catastrophes specifically at their tips. When microtubule growth persistence is reduced, inhibition of depolymerization is sufficient for pseudopod maintenance but not remodeling. We propose that catastrophe inhibition by SLAIN2 and CLASP1 supports mesenchymal cell shape in soft 3D matrices by enabling microtubules to perform a load-bearing function.",
keywords = "+TIPs, 3D matrix, CLIP-170, EB1, Rab6, Rho GTPase, cell migration, ch-TOG, modeling, tumor invasion",
author = "Bouchet, {Benjamin P.} and Ivar Noordstra and {van Amersfoort}, Miranda and Katrukha, {Eugene A.} and Ammon, {York Christoph} and {ter Hoeve}, {Natalie D.} and Louis Hodgson and Marileen Dogterom and Derksen, {Patrick W.B.} and Anna Akhmanova",
note = "Funding Information: We are grateful to Dr. I. Grigoriev for assistance with microscopy; J. van der Beek and J. Bertram for help with cloning and 3D cultures; L. Kapitein and G. Koenderink for critically reading the manuscript; and R. Weinberg, M. Sixt, R. Wedlich-S{\"o}ldner, Y. Mimori-Kiyosue, K. Jiang, L. Cassimeris, I. Barde, D. Trono, J. E. Mertz, O. Pertz, S. Vogel, M. Davidson, D. Piston, P. Sch{\"a}tzle, C. Hoogenraad, E. Bindels, E. Soler, J. Martens, S. Royle, and K. Wolf for the gift of reagents. This work was supported by the Netherlands Organisation for Scientific Research (NWO) through an ALW-VICI grant 865.08.002 and ALW Open Program grant 822.02.002 to A.A., European Research Council (ERC) Synergy Grant 609822 to M.D. and A.A., Marie Sk{\l}odowska-Curie Actions Innovative Training Network PolarNet 675407, Fondation pour la Recherche M{\'e}dicale and Marie Curie International Intra-European Fellowship to B.P.B., NWO/ZonMW-VIDI 016.096.318 to P.W.D., and Foundation Vrienden UMC Utrecht (11.081), the Dutch Cancer Society (KWF-UU-2011-5230 and KWF-UU-2014-7201), and National Cancer Institute grant CA181838 to L.H. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = dec,
day = "19",
doi = "10.1016/j.devcel.2016.11.009",
language = "English (US)",
volume = "39",
pages = "708--723",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",
}
