title: Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells.
abstract: Cytoskeletal remodeling is responsible for cell plasticity and facilitates differentiation, motility and adherence related functions. C3G (RAPGEF1), an exchange factor for Ras family of small GTPases, regulates cytoskeletal reorganization to induce filopodia in epithelial cells and neurite growth in neuroblastoma cells. Here we show that C3G overexpression induces neurite-like extensions (NLE) in MDA-MB-231 and BT549 breast carcinoma cells and not in a variety of other cancer cell lines examined. These processes were actin-rich with nodes, branches and microspikes. C3G associates with the cytoskeleton and its expression enabled stabilization of microtubules. NLE formation was dependent on Rap, Rac and Cdc42. C3G expression was associated with a decrease in cellular β-catenin levels specifically in MDA-MB-231 and BT549 cells. β-Catenin stabilization induced by GSK-3β inhibition, or coexpression of β-catenin, reduced C3G induced NLE formation. Time lapse analysis showed reduced motility of C3G expressing cells compared to GFP expressing cells. Our results suggest that C3G overexpression can induce phenotypic characteristics of neuronal cells in highly invasive breast cancer cells and inhibit their motility.
authors.affiliation: Centre for Cellular and Molecular Biology (CSIR), Uppal Road, Hyderabad 500007, India.
authors.forename: Kunal
authors.initials: K
authors.lastname: Dayma
authors.forename: Vegesna
authors.initials: V
authors.lastname: Radha
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D016501:Neurites / Q000473:pathology*; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D020735:Guanine Nucleotide-Releasing Factor 2; D051176:beta Catenin; D020764:cdc42 GTP-Binding Protein