Claire Brown - McGill University

Cell migration is fundamental to normal biological processes such as development, the immune response and wound healing. However, when cell migration is not regulated properly it can lead to pathological conditions such as cancer metastasis. Cell adhesions form between the extracellular matrix (ECM) and the internal cellular cytoskeleton creating structures required for cell movement. Adhesions are tightly regulated in space and time across the moving cell. For example, they form dynamic anchor points at the front of the cell so it can pull forward and adhesions at the cell rear that need to disassemble allowing for forward cell progression.

This presentation will focus on advanced microscopy techniques and their application to study the adhesion adaptor protein paxillin. Paxillin is an adaptor protein that plays a key role bringing structural and signaling proteins to sites of adhesion. We have been interested in a key paxillin phosphorylation site, serine 273 (S273) that is known to regulate adhesion dynamics. Our work has identified dynamic subdomains within individual adhesions where paxillin interacts and co-binds with one of its binding partners in a kinase-dependent manner. This interaction and kinase activity is required for effective cell migration.

In other work, we have implicated Lipoma Preferred Partner (LPP) as an important mechanosensitive integrator of TGFβ-mediated breast cancer cell migration and invasion. Data will be presented showing that LPP plays a role in regulating cancer cell migration and adhesion dynamics in response to TGFβ stimulation. This regulation requires LPP binding to the actin cytoskeleton which in turn regulates tension across individual adhesions to regulate cell migration. Our work also shows that LPP functions as a mechanosensor to distinguish between substrates of different stiffness and regulates when cells migrate versus invade.

Preliminary data from new developments in the lab will be presented including an invitro assay of cancer metastasis in the brain and expansion microscopy combined with super-resolution STED microscopy of paxillin within adhesions.