Interaction of lifeguard (LFG/FAIM2) with phosphoinositides is associated with altered intracellular calcium homeostasis in breast cancer cells

Lifeguard (LFG/FAIM2) is an anti-apoptotic transmembrane protein implicated in apoptosis resistance and breast cancer progression. However, the molecular mechanisms underlying its biological function remain incompletely understood. In the present study, we investigated potential interactions between LFG and phosphoinositides in the breast cancer cell line MDA-MB-231. Using membrane lipid strip and phosphoinositide (PIP) array assays, we observed binding signals between LFG and several phosphoinositide species, indicating potential lipid-binding preferences under the experimental conditions employed. Because phosphoinositides participate in intracellular calcium signaling pathways, we next examined whether reduced LFG expression was associated with alterations in intracellular calcium homeostasis. Using a fluorescence-based calcium assay, we found that siRNA-mediated downregulation of LFG was associated with increased intracellular calcium-associated fluorescence. Overall, our exploratory findings suggest that LFG may participate in phosphoinositide-associated signaling and intracellular calcium homeostasis in the breast cancer cell model examined. Further studies will be required to validate these observations, determine the underlying molecular mechanisms, and assess their potential relevance for apoptosis regulation and breast cancer progression.