Cortactin affects cell migration by regulating intercellular adhesion and cell spreading.
Cortactin is an F-actin binding protein that stabilizes F-actin networks and promotes actin polymerization by activating the Arp2/3 complex. Overexpression of cortactin, as observed in several human cancers, stimulates cell migration, invasion, and experimental metastasis; however, the underlying mechanism is not understood. To investigate the importance of cortactin in cell migration, we downregulated its expression using RNA interference (RNAi). Stable downregulation of cortactin in HBL100 breast epithelial cells resulted in (i) decreased cell migration and invasion, (ii) enhanced cell-cell adhesion, and (iii) accelerated cell spreading. These phenotypic changes were reversed by expression of RNAi-resistant mouse cortactin. Cortactin colocalized with cadherin and beta-catenin in adherens junctions, consistent with its role in intercellular adhesion. Remarkably, cortactin deficiency did not affect lamellipodia formation. Instead, downregulation of cortactin in human squamous carcinoma cells that overexpress cortactin changed the cytoskeletal organization. We conclude that increased levels of cortactin, as found in human carcinomas, promote cell migration and invasion by reducing cell spreading and intercellular adhesive strength.
van Rossum
Agnes G S H
AG
Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
Moolenaar
Wouter H
WH
Schuuring
Ed
E
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000032:analysis / Q000378:metabolism; D022005:Adherens Junctions / Q000737:chemistry; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology*; D051356:Cortactin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D062793:Occludin; D034741:RNA, Small Interfering / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016596:Vinculin / Q000032:analysis / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D015820:Cadherins; D051356:Cortactin; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D034741:RNA, Small Interfering; D051176:beta Catenin; D016596:Vinculin; D004815:Epidermal Growth Factor; D013755:Tetradecanoylphorbol Acetate