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.
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Bouchet
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Ivar
authors.initials: I
authors.lastname: Noordstra
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Miranda
authors.initials: M
authors.lastname: van Amersfoort
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Katrukha
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: York-Christoph
authors.initials: YC
authors.lastname: Ammon
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Ter Hoeve
authors.affiliation: Department of Anatomy and Structural Biology, Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Hodgson
authors.affiliation: Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ ,Delft, The Netherlands.
authors.forename: Marileen
authors.initials: M
authors.lastname: Dogterom
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Patrick W B
authors.initials: PWB
authors.lastname: Derksen
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007399:Interphase; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D058105:Polymerization; D011554:Pseudopodia / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: C497850:CLASP1 protein, human; D008869:Microtubule-Associated Proteins; C561112:SLAIN2 protein, human; D003094:Collagen; D020741:rho GTP-Binding Proteins
keywords: +TIPs; 3D matrix; CLIP-170; EB1; Rab6; Rho GTPase; cell migration; ch-TOG; modeling; tumor invasion