Dietary oleic acid-induced CD36 promotes cervical cancer cell growth and metastasis via up-regulation Src/ERK pathway.

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.

• Authors: Ping Yang, Chunxiao Su, Xuan Luo, Han Zeng, Lei Zhao, Li Wei, Xiaoyu Zhang, Zac Varghese, John F Moorhead, Yaxi Chen, Xiong Z Ruan
• Journal: Cancer letters (Cancer Lett) Vol. 438 Pg. 76-85 (12 01 2018) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 30213558 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• CD36 Antigens
• Olive Oil
• Oleic Acid
• src-Family Kinases

Topics

• Animals
• CD36 Antigens (genetics, metabolism)
• Cell Proliferation (drug effects, genetics)
• Diet
• Female
• HeLa Cells
• Humans
• Kaplan-Meier Estimate
• MAP Kinase Signaling System (drug effects, genetics)
• Mice, Inbred BALB C
• Mice, Nude
• Oleic Acid (administration & dosage, pharmacology)
• Olive Oil (administration & dosage, pharmacology)
• Transcriptional Activation (drug effects)
• Tumor Burden (drug effects, genetics)
• Up-Regulation (drug effects, genetics)
• Uterine Cervical Neoplasms (genetics, metabolism, pathology)
• Xenograft Model Antitumor Assays (methods)
• src-Family Kinases (genetics, metabolism)