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Cited by 718Cancer, Lipids, and MetabolismLipid metabolism and biosynthesisSphingolipid Metabolism and Signaling

The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

Fatty acid synthesis: a potential selective target for antineoplastic therapy

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Kuhajda, F P, Jenner, K, Wood, F D, Hennigar, R A, Jacobs, L B, Dick, J D, Pasternack, G R·1994·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.91.14.6379PMC PMC44205
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Abstract

OA-519 is a prognostic molecule found in tumor cells from breast cancer patients with markedly worsened prognosis. We purified OA-519 from human breast carcinoma cells, obtained its peptide sequence, and unambiguously identified it as fatty acid synthase through sequence homology and enzymology. Tumor fatty acid synthase is an approximately 270-kDa polypeptide which specifically abolished immunostaining of human breast cancers by anti-OA-519 antibodies. Tumor fatty acid synthase oxidized NADPH in a malonyl-CoA-dependent fashion and synthesized fatty acids composed of 80% palmitate, 10% myristate, and 10% stearate from acetyl-CoA, malonyl-CoA, and NADPH with a specific activity of 624 nmol of NADPH oxidized per min per mg. Tumor cell lines with elevated fatty acid synthase showed commensurate increases in incorporation of [U-14C]acetate into acylglycerols demonstrating that fatty acid synthase increases occur in the context of overall increases in endogenous fatty acid synthesis. Cerulenin inhibited acylglycerol synthesis in tumor cells and fibroblast controls in a dose-dependent fashion and also caused a growth inhibition which generally paralleled the level of endogenous fatty acid synthesis. Supraphysiologic levels of palmitate, 14 microM in dimethyl sulfoxide, significantly reversed the growth inhibition caused by cerulenin at concentrations of up to 5 micrograms/ml, indicating that cerulenin-mediated growth inhibition was due to fatty acid synthase inhibition.

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Crossref · 10.1073/pnas.91.14.6379

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Metadata

Authors
Kuhajda, F. P., Jenner, K., Wood, F. D., Hennigar, R. A., Jacobs, L. B., Dick, J. D., & Pasternack, G. R.
Affiliations
Johns Hopkins University (US)
ORCID
Hennigar, R A
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1994-07-05
Volume
91
Issue
14
Pages
6379-6383
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.91.14.6379
PMC
PMC44205
OpenAlex
W2090846942
Cited by
705
References
26
Citations by year
2026: 13 · 2025: 13 · 2024: 12 · 2023: 32 · 2022: 33 · 2021: 30 · 2020: 19 · 2019: 29 · 2018: 18 · 2017: 31 · 2016: 39 · 2015: 28 · 2014: 38 · 2013: 33 · 2012: 36
FWCI
3.94
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
fatty acid synthase, breast cancer, cerulenin, antineoplastic therapy, fatty acid synthesis, palmitate, NADPH oxidation, malonyl-CoA, tumor growth inhibition
MeSH terms
Acetates, Antibodies, Antigens, Neoplasm, Blood Proteins, Breast Neoplasms, Carbon Radioisotopes, Cell Division, Cell Line, Cerulenin, Fatty Acids, Female, Haptoglobins, Humans, Immunohistochemistry, Kinetics, Malonyl Coenzyme A, Palmitic Acids, Prognosis, Tumor Cells, Cultured, Biomarkers, Tumor, Drug Design, Palmitic Acid, Fatty Acid Synthases

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