OxLDL as an Inducer of a Metabolic Shift in Cancer Cells
| Autor: | Yvonne Oligschlaeger, Annemarie Westheim, Tom Houben, Tulasi Yadati, Rianne D. W. Vaes, Steven W.M. Olde Damink, Lingling Ding, Albert V. Bitorina, Ronit Shiri-Sverdlov, Jan Theys |
|---|---|
| Přispěvatelé: | Moleculaire Genetica, RS: NUTRIM - R2 - Liver and digestive health, Precision Medicine, RS: GROW - R2 - Basic and Translational Cancer Biology, Surgery, MUMC+: MA Heelkunde (9) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Pancreatic cancer cells autophagy OXIDIZED LDL LOW-DENSITY-LIPOPROTEIN HIF-1α HYPOXIA medicine.disease_cause COLORECTAL-CANCER chemistry.chemical_compound Western blot Internal medicine medicine Glycolysis OXIDATIVE STRESS metabolic switch RISK oxLDL medicine.diagnostic_test NONALCOHOLIC STEATOHEPATITIS HIF-1 alpha Autophagy PROLIFERATION Lipid metabolism Endocrinology HIF1A Oncology chemistry CARDIOVASCULAR-DISEASE Low-density lipoprotein Cancer cell lipids (amino acids peptides and proteins) Oxidative stress Research Paper |
| Zdroj: | Journal of Cancer Journal of Cancer, 12(19), 5817-5824. Ivyspring International Publisher |
| ISSN: | 1837-9664 |
| Popis: | Recent evidence established a link between disturbed lipid metabolism and increased risk for cancer. One of the most prominent features related to disturbed lipid metabolism is an increased production of oxidized low-density-lipoproteins (oxLDL), which results from elevated oxidative stress. OxLDL is known to have detrimental effects on healthy cells and plays a primary role in diseases related to the metabolic syndrome. Nevertheless, so far, the exact role of oxLDL in cancer cell metabolism is not yet known. To examine changes in metabolic profile induced by oxLDL, pancreatic KLM-1 cells were treated with oxLDL in a concentration- (25 or 50 mu g/ml) and/or time-dependent (4 hr or 8 hr) manner and the impact of oxLDL on oxygen consumption rates (OCR) as well as extracellular acidification rates (ECAR) was analyzed using Seahorse technology. Subsequently, to establish the link between oxLDL and glycolysis, stabilization of the master regulator hypoxia-inducible factor 1-alpha (HIF-1 alpha) was measured by means of Western blot. Furthermore, autophagic responses were assessed by measuring protein levels of the autophagosomal marker LC3B-II. Finally, the therapeutic potential of natural anti-oxLDL IgM antibodies in reversing these effects was tested. Incubation of KLM-1 cells with oxLDL shifted the energy balance towards a more glycolytic phenotype, which is an important hallmark of cancer cells. These data were supported by measurement of increased oxLDL-mediated HIF-1 alpha stabilization. In line, oxLDL incubation also increased the levels of LC3B-II, suggesting an elevated autophagic response. Importantly, antibodies against oxLDL were able to reverse these oxLDL-mediated metabolic effects. Our data provides a novel proof-of-concept that oxLDL induces a shift in energy balance. These data not only support a role for oxLDL in the progression of cancer but also suggest the possibility of targeting oxLDL as a therapeutic option in cancer. |
| Databáze: | OpenAIRE |
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