High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner.
High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner.
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高转移性胃癌和乳腺癌细胞以 AMPK 依赖性方式消耗油酸
DOI：
10.1371/journal.pone.0097330
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Gao G
中科院分区：
文献类型：
--
作者：
Li S;Zhou T;Li C;Dai Z;Che D;Yao Y;Li L;Ma J;Yang X;Gao G
胃癌和乳腺癌有明显的向脂肪细胞为主的微环境转移和侵袭的倾向。油酸是一种丰富的单不饱和脂肪酸，由脂肪细胞释放，影响不同的能量代谢反应。油酸对高转移癌细胞的作用及其机制尚不完全清楚。我们报道了油酸活化的蛋白激酶（AMPK）在胃癌HGC-27和乳腺癌MDA-MB-231细胞系中被明显激活。AMPK提高了脂肪酸氧化和ATP产生的速率，从而显著促进了血清剥夺下癌细胞的生长和迁移。AMPK的失活降低了油酸的这些活性。油酸能抑制胃癌SGC7901、乳腺癌MCF-7等低转移癌细胞的生长和存活。AMPK的药理激活通过增加脂肪酸β-氧化来维持ATP水平，从而挽救了细胞活力。这些结果表明，高度转移的癌细胞可能以依赖ampk的方式消耗油酸来维持恶性肿瘤。我们的发现证明了脂肪酸氧化对癌细胞功能的重要贡献。
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.
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