High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner.
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.
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Shuai
S
Li
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Ti
T
Zhou
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Cen
C
Li
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Zhiyu
Z
Dai
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Di
D
Che
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Yachao
Y
Yao
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China.
Lei
L
Li
Department of Physiology, University of Oklahoma, Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Jianxing
J
Ma
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China; Key Laboratory of Functional Molecules from Marine Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou, China.
Xia
X
Yang
Department of Biochemistry, Zhongshan School of Medicine, SunYat-sen University, Guangzhou, China; China Key Laboratory of Tropical Disease Control (SunYat-sen University), Ministry of Education, Guangzhou, China.
Guoquan
G
Gao
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000704:Analysis of Variance; D001391:Azo Compounds; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000503:physiopathology*; D001973:Bromodeoxyuridine; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D019301:Oleic Acid / Q000378:metabolism* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D013274:Stomach Neoplasms / Q000503:physiopathology*; D014280:Triglycerides / Q000378:metabolism
D001391:Azo Compounds; D014280:Triglycerides; D019301:Oleic Acid; D055372:AMP-Activated Protein Kinases; D001973:Bromodeoxyuridine; C011049:oil red O