High Metastaticgastric and Breast Cancer Cells Consume Oleic Acid in an AMPK Dependent Manner

Abstract

Gastric cancer and breast cancer have a clear tendency toward metastasis and invasion to the microenvironment predominantly composed of adipocytes. Oleic acid is an abundant monounsaturated fatty acid that releases from adipocytes and impinges on different energy metabolism responses. The effect and underlying mechanisms of oleic acid on highly metastatic cancer cells are not completely understood. We reported that AMP-activated protein kinase (AMPK) was obviously activated in highly aggressive carcinoma cell lines treated by oleic acid, including gastric carcinoma HGC-27 and breast carcinoma MDA-MB-231 cell lines. AMPK enhanced the rates of fatty acid oxidation and ATP production and thus significantly promoted cancer growth and migration under serum deprivation. Inactivation of AMPK attenuated these activities of oleic acid. Oleic acid inhibited cancer cell growth and survival in low metastatic carcinoma cells, such as gastric carcinoma SGC7901 and breast carcinoma MCF-7 cell lines. Pharmacological activation of AMPK rescued the cell viability by maintained ATP levels by increasing fatty acid β-oxidation. These results indicate that highly metastatic carcinoma cells could consume oleic acid to maintain malignancy in an AMPK-dependent manner. Our findings demonstrate the important contribution of fatty acid oxidation to cancer cell function.

Elongation of Long‐Chain Fatty Acid Family Member 6 (Elovl6)‐Driven Fatty Acid Metabolism Regulates Vascular Smooth Muscle Cell Phenotype Through AMP‐Activated Protein Kinase/Krüppel‐Like Factor 4 (AMPK/KLF4) Signaling

“…Furthermore, palmitate treatment significantly induced the phosphorylation of AMPK, ACC, and p53, increased the expression of p21, and decreased the phosphorylation of mTOR (Figure D). In contrast, oleate treatment decreased total protein levels of AMPK, ACC, and p53 and p21, and increased total mTOR levels, as previously reported, and as such, levels of phosphorylated form of AMPK, ACC, and p53 were decreased, and levels of phosphorylated form of mTOR were increased (Figure D). A simultaneous stimulation with palmitate and oleate consistently showed that each of these 2 LCFAs antagonizes the effects of the other (Figure A through D).…”

Phospholipase A2 regulation of lipid droplet formation

“…These cells also show upregulation of their β-oxidation related genes and repression of the de novo lipogenesis genes [51]. This is in accordance with other studies showing that the sole overexpression of group X sPLA 2 in cultured pre-adipocyte cells results in decreased transcription of genes encoding for lipogenic proteins such as SREBP-1c, fatty acid synthase or PPARγ [141]. Inhibition of fatty acid β-oxidation with etomoxir also reduces LD formation in response to group X sPLA 2 , highlighting the seemingly odd circumstance that anabolic -neutral lipid formation and storage in LD-and catabolic -β-oxidation of fatty acids-processes take place simultaneously.…”

Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular Bioenergetic Function in Breast Cancer Cells

“…OA showed a biphasic stimulation (at 0.9 μM) followed by an inhibition at 3.5–9 μM in MDA‐MB‐231 cells [Rose and Connolly, ]. On the other hand, treatment of MDA‐MB‐231 cells with 400 μM BSA‐bound oleic acid increased cell viability and stimulated OCR in without affecting MCF‐7 cells [Li et al, ].…”