Abstract 4326: The potential role of IMP-3 and PDPN in invadopodia formation and collective cancer invasion: Anti-invadopodia therapy as a therapeutic target

Abstract

Abstract Better understanding the mechanisms underlying the metastatic process is essential to developing novel targeted therapeutics. Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are actin-rich structures that have the ability to degrade the underlying extracellular matrix (ECM) and promote cell invasion. However, many questions concerning the mechanisms of invadopodia formation, regulation and function remain open to debate. Meanwhile, invasion of cells into the surrounding tissue and destruction of normal tissue architecture are two hallmarks of malignant tumors. Morphologically, two patterns of tumor invasion can be distinguished; single cell and collective cell invasion. The invasion of single cells and collective cells is often correlated with dramatic changes in the expression and function of adhesive and regulatory proteins. These changes are reminiscent of early developmental processes when cells acquire a migratory, mesenchymal phenotype. Currently, the role of invadopodia in collective cancer invasion is completely unknown. In the present study, we reveal that insuline-like growth factor-II mRNA-binding protein-3 (IMP-3) associated with invadopodial infiltration and collective cancer invasion through podoplanin (PDPN) mRNA stabilization as a component of invadopodia, suggesting that invadopodia plays a pivotal role in invasive front of collective cancer invasion and thereby involved the cancer metastasis. This finding, combined with other investigations into the mechanisms of invadopodia formation, reveal clinically-relevant targets for intervention in invadopodia, including IMP-3 and PDPN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4326. doi:1538-7445.AM2012-4326