Plasma membrane stress can cause damage to the plasma membrane, both when imposed by the extracellular environment and by enhanced oxidative stress. Cells cope with these
injuries by rapidly activating their plasma membrane repair system, which is triggered by Ca(2+) influx at the
wound site. The repair system is highly dynamic, depends on both
lipid and
protein components, and include cytoskeletal reorganization, membrane replacements, and membrane fusion events.
Cancer cells experience enhanced membrane stress when navigating through dense extracellular matrix, which increases the frequency of membrane
injuries. In addition, increased motility and oxidative stress further increase the risk of plasma membrane lesions.
Cancer cells compensate by overexpressing
Annexin proteins including
Annexin A2 (ANXA2).
Annexin family members can facilitate membrane fusion events and wound healing by binding to negatively charged
phospholipids in the plasma membrane. Plasma membrane repair in
cancer cells depends on ANXA2
protein, which is recruited to the
wound site and forms a complex with the Ca(2+)-binding EF-hand
protein S100A11. Here they regulate actin accumulation around the
wound perimeter, which is required for
wound closure. In this review, we will discuss the requirement for
Annexins,
S100 proteins and actin cytoskeleton in the plasma membrane repair response of
cancer cells, which reveals a novel avenue for targeting metastatic
cancers.