Dr Sandrine ETIENNE-MANNEVILLE (Cell Polarity, Migration and Cancer Unit, Institut Pasteur, Paris, France) will give a seminar on October 12, 2012 entitled "Maintenance and dynamics of adherens junctions during collective migration".
Date: Friday, 12 October 2012
Time: 3:30 p.m.
Venue: Seminar Room 5, LG1/F, Laboratory Block, Faculty of Medicine Building 21 Sassoon Road, Pokfulam, Hong Kong
Abstract: Collective cell migration is crucial during development as well as in adult organisms where it participates, for instance, in tissue renewal or wound healing. In cancer, cells migrate as groups or chains to invade the surrounding tissue promoting tumor spreading and metastasis. Our aim is to elucidate the molecular mechanisms that control cell migration and to determine how alterations of these mechanisms may lead to the abnormal migration of cancer cells.
Astrocytes are major glial cells of the central nervous system, where they help the neurons to develop, grow and function properly. In response to cerebral disease or lesion, astrocytes migrate in a tightly controlled and collective manner towards inflammatory sites where they participate to the formation of the glial scar. Astrocytes or their precursors give rise to the majority of cerebral tumors, the gliomas. The most malignant forms of these tumors are extremely invasive which renders them difficult to treat. We use primary astrocytes and glioma cells to study the mechanisms of collective migration.
As cells migrate collectively, intercellular junctions maintain the integrity of the cell monolayer while allowing differential movement and rearrangements of adjacent cells. In astrocytes, intercellular contacts are mainly formed by N-cadherin-mediated adherens junctions. Downregulation of N-cadherin is frequently observed in astrocyte derived tumors and lead to the perturbation of cell polarity and to an increased cell velocity. We have analyzed the dynamics of N-cadherin during 2D and 3D collective migration of astrocytes. We show that junctions undergo a continuous retrograde movement associated with the rearward flow of actin fibers. At the cell rear, adherens junctions are disassembled and N-cadherin is endocytosed. To compensate for the continuous rearward flow of adherens junctions, N-cadherin is recycled and transported back to the leading edge before being incorporated into new adherens junctions at the front of adjacent cells. This global turnover of cadherin complexes allows the cells to maintain stable, strong and yet very adaptable cellular contacts and thus favors cooperation between adjacent cells and collective directed movement. Investigating the molecular mechanisms responsible for the dynamics of cadherin complexes at the front, sides and rear of migrating cells, we found that the tumor suppressor p120catenin, which is strongly downregulated in highly invasive gliomas, plays a central role in the regulation of adherens junction dynamics, and thereby control the speed and directionality of collectively migrating cells.
Croucher-Pasteur Exchange Programme:
In collaboration with the International Affairs Department of Institut Pasteur and the Croucher Foundation, the Centre is establishing an exchange programme for students and post-doctoral fellows resident in Hong Kong in order to strengthen the scientific collaboration between Hong Kong and France. A 2 to 3 year scholarship covering travel, living and university registration expenses will be available for students and post-doctoral fellows resident in Hong Kong wishing to perform research work in laboratories of Institut Pasteur Paris. A lecture series of Pasteur scientists is organised to enable Hong Kong students to meet personally principal investigators from Institut Pasteur, know their scientific work and prospects of pursuing scientific work in their laboratories.