Type IV P-Type ATPases: Recent Updates in Cancer Development, Progression, and Treatment

SIMPLE SUMMARY: Lipids are the main structural component of cellular membranes; they play an essential role in cellular functions. For the growth and progression of cancer, tumor cells require lipid-related metabolic and structural adaptations, such as altered lipid membrane composition, which is in part regulated by lipid flippases. Type IV P-type ATPases (P4-ATPases), the main class of flippases, are responsible for membrane lipid asymmetry, and thus they are closely involved in cancer-related lipid changes. Lately, flippases have gained more attention regarding the pathobiology of human disease. This review focuses on recent publications discussing the role of P4-ATPases in cancer development, progression, and prospective treatment. ABSTRACT: Adaptations of cancer cells for survival are remarkable. One of the most significant properties of cancer cells to prevent the immune system response and resist chemotherapy is the altered lipid metabolism and resulting irregular cell membrane composition. The phospholipid distribution in the plasma membrane of normal animal cells is distinctly asymmetric. Lipid flippases are a family of enzymes regulating membrane asymmetry, and the main class of flippases are type IV P-type ATPases (P4-ATPases). Alteration in the function of flippases results in changes to membrane organization. For some lipids, such as phosphatidylserine, the changes are so drastic that they are considered cancer biomarkers. This review will analyze and discuss recent publications highlighting the role that P4-ATPases play in the development and progression of various cancer types, as well as prospects of targeting P4-ATPases for anti-cancer treatment.