期刊
CANCER LETTERS
卷 438, 期 -, 页码 76-85出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.09.006
关键词
High olive oil diet; Fatty acid transporter; Cell proliferation; Cell migration; Tyrosine kinase
类别
资金
- National Natural Science Foundation of China [81570517, 31571210, 81390354]
- Chongqing Research Program of Basic Research and Frontier Technology [cstc2015jcyjBX0044]
- Science and Technology Research Program of Chongqing Municipal Education Commission [KJ1702029]
- Program for Innovation Team of Higher Education in Chongqing, China [CXTDX201601015]
Epidemiological and experimental studies have revealed strong associations between dietary lipids and cancer risk. However, the molecular mechanisms underlying the effects of dietary fatty acids on the genesis and progression of cancer have been poorly explored. In this study, we found that a high olive oil diet stimulated cervical cancer (CC) carcinogenesis, and oleic acid (OA), the main lipid in olive oil, was associated with increased malignancy in HeLa cells. OA up-regulated the expression of CD36, which is the best characterized fatty acid transporter. Inhibiting CD36 prevented the tumor-promoting effects of OA, while overexpressing CD36 mimicked the effects of OA. Clinically, CD36 expression was positively correlated with tumor progression and poor prognosis in patients with CC. Furthermore, OA induced Src kinase and downstream ERK1/2 pathway activation in a CD36-dependent manner. Pretreatment of HeLa cells with an Src kinase inhibitor largely blocked the tumor promoting effect of OA. Our findings suggest that dietary OA exerts a stimulatory effect on CC growth and metastasis, and CD36 might be a promising therapeutic target that acts against CC through an Src/ERK-dependent signaling pathway.
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