AI Article Synopsis
- Oncogene-induced metabolic changes are crucial for pancreatic cancer (PDAC) progression, particularly in how they relate to metastasis.
- Excess fatty acids and lipid storage in lipid droplets, regulated by the oncogene KRAS and hormone-sensitive lipase (HSL), play a significant role in fueling tumor invasion.
- Targeting the KRAS-HSL pathway may be a promising strategy for developing treatments that reduce PDAC metastasis.
Article Abstract
Oncogene-induced metabolic reprogramming is a hallmark of pancreatic cancer (PDAC), yet the metabolic drivers of metastasis are unclear. In PDAC, obesity and excess fatty acids accelerate tumor growth and increase metastasis. Here, we report that excess lipids, stored in organelles called lipid droplets (LD), are a key resource to fuel the energy-intensive process of metastasis. The oncogene KRAS controlled the storage and utilization of LD through regulation of hormone-sensitive lipase (HSL), which was downregulated in human PDAC. Disruption of the KRAS-HSL axis reduced lipid storage, reprogrammed tumor cell metabolism, and inhibited invasive migration and metastasis . Finally, microscopy-based metabolic analysis revealed that migratory cells selectively utilize oxidative metabolism during the process of migration to metabolize stored lipids and fuel invasive migration. Taken together, these results reveal a mechanism that can be targeted to attenuate PDAC metastasis. SIGNIFICANCE: KRAS-dependent regulation of HSL biases cells towards lipid storage for subsequent utilization during invasion of pancreatic cancer cells, representing a potential target for therapeutic intervention..
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669720 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-20-1255 | DOI Listing |
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