Prevention of dietary-fat-fueled ketogenesis attenuates BRAF V600E tumor growth Journal Article

   


Authors: Xia, S.; Lin, R.; Jin, L.; Zhao, L.; Kang, H. B.; Pan, Y.; Liu, S.; Qian, G.; Qian, Z.; Konstantakou, E.; Zhang, B.; Dong, J. T.; Chung, Y. R.; Abdel-Wahab, O.; Merghoub, T.; Zhou, L.; Kudchadkar, R. R.; Lawson, D. H.; Khoury, H. J.; Khuri, F. R.; Boise, L. H.; Lonial, S.; Lee, B. H.; Pollack, B. P.; Arbiser, J. L.; Fan, J.; Lei, Q. Y.; Chen, J.
Article Title: Prevention of dietary-fat-fueled ketogenesis attenuates BRAF V600E tumor growth
Abstract: Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice. Treatment with hypolipidemic agents to lower circulating acetoacetate levels or an inhibitory homolog of acetoacetate, dehydroacetic acid, to antagonize acetoacetate-BRAF V600E binding attenuated BRAF V600E tumor growth. These findings reveal a signaling basis underlying a pathogenic role of dietary fat in BRAF V600E-expressing melanoma, providing insights into the design of conceptualized “precision diets” that may prevent or delay tumor progression based on an individual's specific oncogenic mutation profile. © 2017 Elsevier Inc.
Keywords: cancer risk; cancer prevention; cancer therapy; cancer metabolism; braf v600e; ketogenesis; acetoacetate; dehydroacetic acid; dietary fat; precision diet
Journal Title: Cell Metabolism
Volume: 25
Issue: 2
ISSN: 1550-4131
Publisher: Elsevier Inc.  
Date Published: 2017-02-07
Start Page: 358
End Page: 373
Language: English
DOI: 10.1016/j.cmet.2016.12.010
PROVIDER: scopus
PMCID: PMC5299059
PUBMED: 28089569
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85009468530&doi=10.1016%2fj.cmet.2016.12.010&partnerID=40&md5=2a50408bcd6f6c11e8bb86c224bbe1af
Notes: Article -- Export Date: 2 March 2017 -- Source: Scopus
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MSK Authors
  1. Taha Merghoub
    364 Merghoub
  2. Omar Ibrahim Abdel-Wahab
    573 Abdel-Wahab
  3. Young Rock Chung
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