Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and metastasis via up-regulation Src/ERK pathway.
Yang P1, Su C1, Luo X1, Zeng H1, Zhao L1, Wei L1, Zhang X1, Varghese Z2, Moorhead JF2, Chen Y3,Ruan XZ4.
Cancer Lett. 2018 Dec 1;438:76-85. doi: 10.1016/j.canlet.2018.09.006. Epub 2018 Sep 11.
PMID:30213558 DOI:10.1016/j.canlet.2018.09.006
Abstract
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.