title: WIP promotes in-vitro invasion ability, anchorage independent growth and EMT progression of A549 lung adenocarcinoma cells by regulating RhoA levels.
abstract: Cancer cell migration and invasion involves actin cytoskeleton reorganization, which is regulated by the WASP (Wiskott Aldrich Syndrome Protein) family of proteins such as WASP, N-WASP (Neural-WASP) and WASP interacting protein (WIP). In this study, we found that the expression of WIP was significantly upregulated in metastatic A5-RT3 cells compared to its parental non-tumorigenic HaCaT cells. Using A549 human lung adenocarcinoma cell line as the model system, we found that WIP regulates cell invasion, proliferation and anchorage-independent growth. Expression of WIP was enhanced during TGF-β1 induced epithelial-mesenchymal transition (EMT) and overexpression of WIP accelerated EMT while knocking down WIP attenuated EMT associated morphological changes. Knocking down WIP expression in A549 cells significantly reduced RhoA levels and WIP was found to interact with RhoA suggesting that WIP might be executing its function by regulating RhoA. Acquisition of invasive, proliferative properties and anoikis resistance is the central step in metastasis indicating a novel function of WIP in cancer progression.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Amrita
authors.initials: A
authors.lastname: Salvi
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore. Electronic address: thirumaran@ntu.edu.sg.
authors.forename: Thirumaran
authors.initials: T
authors.lastname: Thanabalu
mesh_terms: D000072283:A549 Cells; D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053773:Transforming Growth Factor beta1; C109903:WIPF1 protein, human; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein
keywords: Actin cytoskeleton; RhoA; TGF-β1 induced EMT; WIP