Annexins are instrumental for efficient plasma membrane repair in cancer cells.
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.
Membrane Integrity Group, Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark.
Stine Prehn
SP
Lauritzen
Membrane Integrity Group, Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark.
Theresa Louise
TL
Boye
Membrane Integrity Group, Unit for Cell Death and Metabolism, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark. Electronic address: jnl@cancer.dk.
Jesper
J
Nylandsted
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017302:Annexins / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002462:Cell Membrane / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009418:S100 Proteins / Q000378:metabolism; D014945:Wound Healing
D017302:Annexins; D009418:S100 Proteins
Actin cytoskeleton; Annexin A2; Annexins; Breast cancer; Cancer; Metastasis; Plasma membrane repair; S100 proteins; S100A11