Abstract 3052 A bridge-like lipid transport protein controls plasma membrane fluidity and breast cancer aggressiveness

Lipid transport proteins (LTPs) facilitate nonvesicular lipid exchange between cellular compartments and have critical roles in lipid homeostasis.A recently identified family of bridge-like LTPs (BLTPs) is thought to form lipid-transporting conduits between organelles.One, BLTP2, is conserved across species but its function is not known.We find that BLTP2 regulates plasma membrane (PM) fluidity by increasing phosphatidylethanolamine (PE) levels in the PM.BLTP2 localizes to endoplasmic reticulum (ER)-PM contact sites, and transports PE in vivo, suggesting it drives PE movement from ER to PM.We discovered that BLTP2 works in parallel with another pathway that regulates intracellular PE distribution and PM fluidity.BLTP2 expression correlates with breast cancer aggressiveness.We find that BLTP2 facilitates growth of a triple negative breast cancer cell line MDA-MB-231 and sustains its aggressiveness in an in vivo model of metastasis, suggesting maintenance of PM fluidity by BLTP2 may be critical for tumorigenesis in humans.Recent evidence suggests BLTP2 may also facilitate the growth of MDA-MB-231 cells by suppressing ferroptosis, perhaps by affecting the PE distribution or metabolism.