Abstract A156: CrkI and CrkII adaptor proteins promote invasiveness and metastasis via epithelial-mesenchymal transition (EMT) in A549 lung adenocarcinoma cells

Epithelial-to-mesenchymal transition (EMT) is a leading phenomenon implicated in morphogenesis, invasiveness and metastasis of cancer cells. Likewise, Crk adaptor proteins described to promote an epithelial-mesenchymal-like transition and are required for HGF-mediated cell spreading and breakdown of epithelial adherens junctions in MDCK kidney epithelial cells. In this study we show that overexpression of CrkI and CrkII; members of Crk adaptor family of signalling proteins in A549 lung adenocarcinoma cells induce morphological changes resemble mesenchymal cells with high motility and invasiveness potential in both in vitro and in vivo. Furthermore, CrkI and CrkII both induce EMT but mostly through different pathways, while CrkI had a significant effect on TGFβ1-SMAD pathway which might be the inducer of EMT, more than CrkII, CrkII which had a higher Rac1 activity in the other hand showed a prominent effect on the expression of transcriptional factors regulating EMT like Snail and Slug, leading to almost total loss of the cell-cell adhesion glycoprotein E-cadherin expression, as well as remarkable increases in the production of extracellular matrix metalloproteinase (MMP) 2. These effects were opposed by inhibiting Rac1 activity. In conclusion, we could describe that CrkI and CrkII have a differential effect on the EMT process via activating Rac1, MMPs production, and the potential effect on TGF-β signalling, highlighting novel regulatory mechanisms of the adaptor protein Crk, and its involvement in cancer metastasis. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A156. Citation Format: Aiman Elmansuri, Mishie Tanino, Roshan Mahabir, Lei Wang, Masumi Tsuda, Taichi Kimura, Hiroshi Nishihara, Shinya Tanaka. CrkI and CrkII adaptor proteins promote invasiveness and metastasis via epithelial-mesenchymal transition (EMT) in A549 lung adenocarcinoma cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A156.