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This study reveals that pancreatic cancer cells use lysosomal acid lipase (LAL) to break down stored lipids in lipid droplets, which supports their ability to invade surrounding tissues. The researchers found that this lipid breakdown process occurs specifically at invadopodia, the cellular structures that degrade the extracellular matrix, where it provides both local energy in the form of ATP and membrane cholesterol needed for invasion. The process regulates both cellular energy metabolism and membrane composition through changes in cholesterol and phospholipid levels.
Why it matters
Understanding how cancer cells metabolically support invasion could reveal new therapeutic targets to prevent metastasis, the leading cause of cancer-related deaths. Targeting lysosomal lipid metabolism might offer a strategy to block pancreatic cancer spread without solely focusing on tumor growth inhibition.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Metabolic vulnerabilities in cancer have been targeted primarily to suppress tumor growth, but less is known about the metabolic requirements for tumor cell invasion. Here we report that lipid catabolism by cytosolic and lysosomal lipases supports pancreatic cancer cell invasion through both overlapping and distinct functional and metabolic mechanisms. Lysosomal acid lipase (LAL)-dependent lipid droplet catabolism promotes invadopodia formation and stabilization, enabling extracellular matrix degradation. In addition to modulating cellular energetics, lipidomics revealed that lipid droplet catabolism regulates cholesterol and membrane phospholipid levels. Using spatially resolved biosensors and cholesterol imaging, we found that lysosomal lipid catabolism occurs at invadopodia and sustains local ATP and membrane cholesterol. These findings identify spatially organized lipid catabolism as a mechanism that couples local energetics and membrane remodeling during the earliest steps of pancreatic cancer cell invasion.