Specific roles of Rac1 and Rac2 in motile functions of HT1080 fibrosarcoma cells.
Rho family proteins are constitutively activated in the highly invasive human fibrosarcoma HT1080 cells. We now investigated the specific roles of Rac1 and Rac2 in regulating morphology, F-actin organization, adhesion, migration, and chemotaxis of HT1080 cells. Downregulation of Rac1 using specific siRNA probes resulted in cell rounding, markedly decreased spreading, adhesion, and chemotaxis of HT1080 cells. 2D migration on laminin-coated surfaces in contrast was not markedly affected. Selective Rac2 depletion did not affect cell morphology, cell adhesion, and 2D migration, but significantly reduced chemotaxis. Downregulation of both Rac1 and Rac2 resulted in an even more marked reduction, but not complete abolishment, of chemotaxis indicating distinct as well as overlapping roles of both proteins in chemotaxis. Rac1 thus is selectively required for HT1080 cell spreading and adhesion whereas Rac1 and Rac2 are both required for efficient chemotaxis.
Niggli
Verena
V
Department of Pathology, University of Bern, Murtenstr. 31, CH-3010 Bern, Switzerland. verena.niggli@pathology.unibe.ch
Schlicht
Dominique
D
Affentranger
Sarah
S
D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000235:genetics; D002633:Chemotaxis / Q000235:genetics; D005354:Fibrosarcoma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*; D000097766:RAC2 GTP-Binding Protein
D034741:RNA, Small Interfering; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein