Phospholipid scramblases TMEM16F and Xkr8 mediate distinct features of phosphatidylserine (PS) externalization and immune suppression to promote tumor growth.

ABSTRACT: The phospholipid scramblases Xkr8 and TMEM16F externalize phosphatidylserine (PS) by distinct mechanisms. Xkr8 is activated by caspase-mediated proteolytic cleavage and, in synergy with the inactivation of P4-ATPase flippases, results in the irreversible externalization of PS on apoptotic cells and an "eat-me" signal for efferocytosis. In contrast, TMEM16F is a calcium-activated scramblase that reversibly externalizes PS on viable cells via the transient increase in intracellular calcium in live cells. The tumor microenvironment (TME) is abundant with exposed PS, resulting from prolonged oncogenic and metabolic stresses and high apoptotic indexes of tumors. Such chronic PS externalization in the TME has been linked to host immune evasion from interactions of PS with inhibitory PS receptors

SUBMITTER: Gadiyar V 

PROVIDER: S-EPMC12592367 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature