title: Positive regulation of migration and invasion by vasodilator-stimulated phosphoprotein via Rac1 pathway in human breast cancer cells.
abstract: This study aimed to investigate the role of the cytoskeleton-associated protein vasodilator-stimulated phosphoprotein (VASP) on the migration and invasion of human breast cancer cells and its relationship to Rac1 which is a member of the Rho family and has been found to be implicated in tumorigenesis, invasion and metastasis. We detected the mRNA and protein expression levels of VASP and Rac1 of the non-invasive breast cancer cell line MCF-7 as well as the invasive cell line MDA-MB-231 by RT-PCR and Western blotting. GST pull-down assay was used to examine the activity of Rac1. Accordingly, the cell invasive migration ability was analyzed in a wound-healing assay (2D) and transwell assays (3D migration and invasion). We then used VASP-siRNA to inhibit the expression of VASP in breast cancer cells in order to study the relationship between the VASP expression level and the invasive migration ability of breast cancer cells. Rac1-siRNA was used to decrease the expression of Rac1, and observe its effect on the VASP expression level together with the migration and invasion ability of MCF-7 and MDA-MB-231 cells. Our results revealed that the invasive breast cancer cell line MDA-MB-231 showed a higher Rac1 activity and VASP expression level compared with the non-invasive MCF-7. Inhibition of Rac1 or VASP by siRNA, respectively, decreased the migration and invasion ability of breast cancer cells and the transfection of Rac1 siRNA-mediated reduction of VASP expression at mRNA and protein levels. Collectively, our data showed that the higher expression level of VASP contributed to a higher invasive migration capacity of human breast cancer cells which was controlled by the Rac1 pathway.
authors.affiliation: Department of Pathology and Pathophysiology, Hubei Provincial Key Laboratory of Allergy and Immune-Related Diseases Centre for Medical Research, School of Medicine, Wuhan University, Hubei, P.R. China.
authors.forename: Guoge
authors.initials: G
authors.lastname: Han
authors.forename: Biao
authors.initials: B
authors.lastname: Fan
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Yongping
authors.initials: Y
authors.lastname: Wang
authors.forename: Huimin
authors.initials: H
authors.lastname: Dong
authors.forename: Yun
authors.initials: Y
authors.lastname: Wei
authors.forename: Shengrong
authors.initials: S
authors.lastname: Sun
authors.forename: Mingbo
authors.initials: M
authors.lastname: Hu
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D000098662:Vasodilator-Stimulated Phosphoprotein; D009240:N-Formylmethionine Leucyl-Phenylalanine; D020830:rac1 GTP-Binding Protein