title: The Rho guanine nucleotide exchange factor Syx regulates the balance of dia and ROCK activities to promote polarized-cancer-cell migration.
abstract: The role of RhoA in promoting directed cell migration has been complicated by studies showing that it is activated both in the front and the rear of migrating cells. We report here that the RhoA-specific guanine nucleotide exchange factor Syx is required for the polarity of actively migrating brain and breast tumor cells. This function of Syx is mediated by the selective activation of the RhoA downstream effector Dia1, the subsequent reorganization of microtubules, and the downregulation of focal adhesions and actin stress fibers. The data argue that directed cell migration requires the precise spatiotemporal regulation of Dia1 and ROCK activities in the cell. The recruitment of Syx to the cell membrane and the subsequent selective activation of Dia1 signaling, coupled with the suppression of ROCK and activation of cofilin-mediated actin reorganization, plays a key role in establishing cell polarity during directed cell migration.
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida, USA.
authors.forename: Justus C
authors.initials: JC
authors.lastname: Dachsel
authors.forename: Siu P
authors.initials: SP
authors.lastname: Ngok
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Lewis-Tuffin
authors.forename: Antonis
authors.initials: A
authors.lastname: Kourtidis
authors.forename: Rory
authors.initials: R
authors.lastname: Geyer
authors.forename: Lauren
authors.initials: L
authors.lastname: Johnston
authors.forename: Ryan
authors.initials: R
authors.lastname: Feathers
authors.forename: Panos Z
authors.initials: PZ
authors.lastname: Anastasiadis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D016764:Cell Polarity; D048430:Cell Shape; D022001:Focal Adhesions / Q000378:metabolism; D000080865:Formins; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D055550:Protein Stability; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D000080865:Formins; D020662:Guanine Nucleotide Exchange Factors; C522397:PLEKHG5 protein, human; D034741:RNA, Small Interfering; D054460:rho-Associated Kinases