Projects / Programmes
Lipid droplets as sources of inflammatory lipid mediators in cancer
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
Cancer, lipids, lipid droplets, metabolism, fat, vnetje, stress response, lipolysis, triglycerides, fatty acids, tumour, immunity, phospholipids, eicosanoids, resolvins, lipid mediators
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
38200 |
PhD Eva Jarc Jovičić |
Biochemistry and molecular biology |
Head |
2020 - 2023 |
67 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
90,682 |
Abstract
Inflammation is tightly linked to tumorigenesis. It can either stimulate or inhibit tumour growth and it defines the tumour invasive potential. Inflammation is also associated with states of persistent overload of lipids, which often lead to chronic inflammation and tissue metabolic dysfunction, increasing the risk for cancer development. Cancer cells have developed various mechanisms that hijack metabolic and inflammatory processes and use them to their own advantage. Notably, cancer cells alter their lipid metabolism and signalling in a way that fosters both inflammation and tumorigenesis. Although lipids are mostly regarded as structural components and energy sources, they are also involved in the regulation of inflammatory processes. Lipid mediators (LMs) are bioactive lipids that are produced in response to inflammatory stimuli by both cancer and immune cells and act on target cells via their cognate G protein-coupled receptors (GPCRs). LMs display distinct effects on inflammation, being either pro-inflammatory or anti-inflammatory. Numerous LMs also affect cancer cell proliferation and invasion by directly binding to cancer cells. LMs are synthesized from polyunsaturated fatty acid (PUFA) precursors, which are localized to distinct cellular lipid pools, including membrane phospholipids and neutral lipids stored in lipid droplets (LDs). LDs are organelles with pleiotropic functions in lipid metabolism and signalling. They accumulate in cancer cells and contribute to the increased resilience of cancer cells to stress. Their roles in inflammation and immunity are emerging and recent studies have revealed that LDs are important sources for LM synthesis in neutrophils and mastocytes. However, the possibility that cancer cell LDs provide PUFAs for LM production, thereby driving both tumourigenesis and inflammation has not been confirmed yet. The major objective of this project is to determine whether LDs are sources for LM production in cancer cells. We aim to define the importance of LD breakdown processes that regulate the release of PUFAs from triglycerides stored within LDs as sources for the production of LMs. By modulating LD turnover using genetic and pharmacological means, we will study the links between LD metabolism and LM production. Mechanistically, our major aim will be to pinpoint the ways in which the major enzymes involved in LD breakdown contribute to the provision of PUFAs for LM production. This will also be the first study to provide a comprehensive lipidomic insight into the connections between the LD and LM lipidome in cancer cells. Finally, we will study the ability of LD-derived LMs to affect the tumourigenic potential of cancer cells and regulate immune cell function. Targeting LDs as a potential major driver of LM production may reduce cancer-associated inflammation and provide new routes for therapeutic intervention.
