291741 The Role of Microtubules and Microtubule-Binding Proteins EB1 and LIC2 in Three-Dimensional Cancer Cell Migration

Monday, October 29, 2012
Hall B (Convention Center )
Nicholaus Trenton, Anjil Giri, Hasini Jayatilaka and Denis Wirtz, Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD

Cell migration is crucial for various types of biological processes, such as embryogenesis, wound healing, inflammatory response, and cancer cell metastasis. The mechanism of cell migration requires synchronization of many events, including polarization of signaling molecules, orientation of the microtubule organizing center towards the direction of migration, and, importantly, the rapid reorganization of actin and microtubule cytoskeleton. Numerous studies have focused on elucidating the role of actin in cell migration; however, recent studies have shown that stabilization of microtubules plays a pivotal role in this process. Most of these studies were performed for cells migrating on flat two-dimensional substrates (2D), but cell migration in vivo predominantly occurs through three-dimensional (3D) hydrogel matrices, and not much is known about the role of microtubules and microtubule-binding-proteins, EB1 and LIC2, for 3D motility. Here we report that microtubule organization and dynamics are critical for 3D cell migration using microtubule depolymerizing drug nocodazole and microtubule stabilizing drug taxol. Moreover, we show that destabilization of microtubules by depletion of EB1 and LIC2 attenuates cell migration by reducing protrusion activity.

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