Nature Cancer· 2026Q1
ANO6-mediated trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer cell growth and immune suppression
- 25citations
- Q1SCImago
- 2026year
Short summary
Cancer cells acquire essential lipids from cancer-associated fibroblasts (CAFs) via membrane transfer (trogocytosis) regulated by ANO6, which also drives immune suppression.
AI-generated from the title and abstract; the full text is not read.
Key points
- Pancreatic cancer cells obtain lipids from CAFs via trogocytosis, a process mediated by CAF plasma membrane transfer.
- ANO6, a phospholipid scramblase in CAFs, is essential for trogocytosis, activated by calcium influx.
- ANO6-dependent trogocytosis transfers lipids, including cholesterol, to PDAC cells, promoting their survival.
- This process also enhances immune suppression by increasing cholesterol transfer to cytotoxic T cells.
AI-generated from the title and abstract; the full text is not read.
Abstract
In pancreatic ductal adenocarcinoma (PDAC), the fibroblastic stroma constitutes most of the tumor mass and is remarkably devoid of functional blood vessels. 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 obtaining 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 CAF trogocytosis regulator required to promote PDAC cell survival. During trogocytosis, cancer cells and CAFs form synapse-like plasma membranes contacts that induce cytosolic calcium influx in CAFs via Orai channels. This influx activates ANO6 and results in phosphatidylserine exposure on CAF plasma membrane initiating trogocytosis and transfer of membrane lipids, including cholesterol, to PDAC cells. Importantly, ANO6-dependent trogocytosis also supports the immunosuppressive function of pancreatic CAFs towards cytotoxic T cells by promoting transfer of excessive amounts of cholesterol. Further, blockade of ANO6 antagonizes tumor growth via disruption of delivery of exogenous cholesterol to cancer cells and reverses immune suppression suggesting a potential new strategy for PDAC therapy.
The authors' abstract, as published at the source. Nature Cancer, 2026 · DOI ↗
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Cancer ResearchBiochemistry, Genetics and Molecular Biology