Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6).

This raises an unresolved question of how PDAC cells obtain essential metabolites and water-insoluble lipids. We have found a critical role for cancer-associated fibroblasts (CAFs) in acquiring and transferring lipids from blood-borne particles to PDAC cells via trogocytosis of CAF plasma membranes.

We have also determined that CAF-expressed phospholipid scramblase anoctamin 6 (ANO6) is an essential regulator of CAF trogocytosis required to promote PDAC cell survival. During trogocytosis, cancer cells and CAFs form synapse-like plasma membrane contacts that induce cytosolic calcium influx in CAFs via Orai channels. This influx activates ANO6 and results in phosphatidylserine exposure on CAF plasma membranes, initiating trogocytosis and transfer of membrane lipids, including cholesterol, to PDAC cells.