Asset Details
Do you wish to reserve the book?
Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer
Do you wish to request the book?
Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer
2016
Overview
In the triple-negative subtype of breast cancer, for which treatment options are limited, overexpression of the MYC oncoprotein is associated with increased sensitivity to growth inhibition by fatty acid oxidation inhibitors, thus pointing to a new therapeutic strategy.
Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor–, progesterone receptor– or human epidermal growth factor 2 receptor–positive (RP) breast cancer
1
,
2
. We and others have shown that MYC alters metabolism during tumorigenesis
3
,
4
. However, the role of MYC in TNBC metabolism remains mostly unexplored. We hypothesized that MYC-dependent metabolic dysregulation is essential for the growth of MYC-overexpressing TNBC cells and may identify new therapeutic targets for this clinically challenging subset of breast cancer. Using a targeted metabolomics approach, we identified fatty acid oxidation (FAO) intermediates as being dramatically upregulated in a MYC-driven model of TNBC. We also identified a lipid metabolism gene signature in patients with TNBC that were identified from The Cancer Genome Atlas database and from multiple other clinical data sets, implicating FAO as a dysregulated pathway that is critical for TNBC cell metabolism. We found that pharmacologic inhibition of FAO catastrophically decreased energy metabolism in MYC-overexpressing TNBC cells and blocked tumor growth in a MYC-driven transgenic TNBC model and in a MYC-overexpressing TNBC patient–derived xenograft. These findings demonstrate that MYC-overexpressing TNBC shows an increased bioenergetic reliance on FAO and identify the inhibition of FAO as a potential therapeutic strategy for this subset of breast cancer.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 59
/ 64/60
/ Cell Proliferation - genetics
/ Energy Metabolism - drug effects
/ Energy Metabolism - genetics
/ Female
/ Gene Expression Regulation, Neoplastic
/ Humans
/ letter
/ Proto-Oncogene Proteins c-myc - biosynthesis
/ Proto-Oncogene Proteins c-myc - genetics
/ Triple Negative Breast Neoplasms - drug therapy
/ Triple Negative Breast Neoplasms - metabolism
