Plasma membrane repair provides a new strategy for targeting metastatic cancer cells

Abstract

Stress induced plasma membrane injuries imposed by mechanical activity and the extracellular environment is a constant threat to cells that they need to cope with to stay alive. This is especially prominent for invasive cancer cells with their increased motility and capacity to navigate through the harsh tumor stroma, which further increases the risk of plasma membrane injury. The impact of these stresses on cancer cell membrane and mechanism by which tumor cells cope with this is poorly understood. Plasma membrane repair (PMR) is triggered by Ca 2+ influx through the injury site. Depending on the cell type and extent of damage, cells use different components including yolk granules, lysosomes, mitochondria and cytoskeleton to help repair the damaged plasma membrane. Here, the involvement of annexins and S100 proteins in PMR will be discussed in light of our recent discovery showing that metastatic cancer cells require S100A11 protein and its binding partner annexin A2 for PMR. This Ca 2+ -triggered protein complex facilitate resealing by modulating polymerization of actin cytoskeleton at the plasma membrane to enable wound closure and excision of damaged membrane. These findings demonstrate that cancer cells depend on efficient PMR, which reveal a new approach for targeting metastatic cancer cells.