WIP promotes in-vitro invasion ability, anchorage independent growth and EMT progression of A549 lung adenocarcinoma cells by regulating RhoA levels

• Main Authors: Salvi, Amrita, Thanabalu, Thirumaran
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2017
• Subjects: WIP; Actin Cytoskeleton
• Online Access: https://hdl.handle.net/10356/86058; http://hdl.handle.net/10220/43930
• Institution: Nanyang Technological University

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.