Injuries to the cell membrane of cancer cells, which are caused from invasive behavior, enhanced membrane dynamic and metabolic stress pose lethal threats to cancer cells. However, cancer cells cope by activating their plasma membrane repair system, which depends on mechanisms to remove damaged membrane by excision, internalization by endocytosis or reorganization of actin around the hole to reseal the wound. Proteins belonging to the annexin family are often found highly expressed in various cancer types and are characterized by their Ca2+-dependent binding to anionic phospholipids in the plasma membrane. Annexin family members share the ability to glue adjacent membranes together during wound healing but our recent results show that they play roles that are more specific in membrane repair by regulation of membrane excision, shedding, and induction of membrane curvature in cancer cells. Our findings open a novel avenue to target cancer cells by compromising annexin mediated plasma membrane repair. Here, novel molecular aspects of targeting the membrane repair system in cancer cells by phenothiazines, which alter plasma membrane properties and sensitize to membrane injury by inhibiting annexin-mediated repair will be presented.
Dr. Jesper Nylandsted is Group Leader at the Danish Cancer Society Research Center in Copenhagen. His work focuses on alternative death pathways and repair mechanisms in cancer cells and novel approaches to target these processes. Using biophysical methods and live cell imaging, his group has revealed fundamental processes in cell death signalling and plasma membrane repair mechanisms of cancer cells.