title: Dia-interacting protein (DIP) imposes migratory plasticity in mDia2-dependent tumor cells in three-dimensional matrices.
abstract: Tumor cells rely upon membrane pliancy to escape primary lesions and invade secondary metastatic sites. This process relies upon localized assembly and disassembly cycles of F-actin that support and underlie the plasma membrane. Dynamic actin generates both spear-like and bleb structures respectively characterizing mesenchymal and amoeboid motility programs utilized by metastatic cells in three-dimensional matrices. The molecular mechanism and physiological trigger(s) driving membrane plasticity are poorly understood. mDia formins are F-actin assembly factors directing membrane pliancy in motile cells. mDia2 is functionally coupled with its binding partner DIP, regulating cortical actin and inducing membrane blebbing in amoeboid cells. Here we show that mDia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. DIP controls mesenchymal/amoeboid cell interconvertability, while CXCL12 induces assembly of mDia2:DIP complexes to bleb cortices in 3D matrices. These results demonstrate how DIP-directed mDia2-dependent F-actin dynamics regulate morphological plasticity in motile cancer cells.
authors.affiliation: Department of Biochemistry, University of Toledo, Health Science Campus, Toledo, Ohio, United States of America.
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Wyse
authors.forename: Jun
authors.initials: J
authors.lastname: Lei
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Nestor-Kalinoski
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Eisenmann
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D054377:Chemokine CXCL12; C491462:DIAPH2 protein, human; D000080865:Formins; D009124:Muscle Proteins; C486062:NCKIPSD protein, human