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Cited by 477

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity

Open access
Vriens, Kim, Christen, Stefan, Parik, Sweta, Broekaert, Dorien, Yoshinaga, Kazuaki, Talebi, Ali, Dehairs, Jonas, Escalona-Noguero, Carmen, Schmieder, Roberta, Cornfield, Thomas, Charlton, Catriona, Romero-Pérez, Laura, Rossi, Matteo, Rinaldi, Gianmarco, Orth, Martin F., Boon, Ruben, Kerstens, Axelle, Kwan, Suet Ying, Faubert, Brandon, Méndez-Lucas, Andrés, Kopitz, Charlotte C., Chen, Ting, Fernandez-Garcia, Juan, Duarte, João A. G., Schmitz, Arndt A., Steigemann, Patrick, Najimi, Mustapha, Hägebarth, Andrea, Van Ginderachter, Jo A., Sokal, Etienne, Gotoh, Naohiro, Wong, Kwok-Kin, Verfaillie, Catherine, Derua, Rita, Munck, Sebastian, Yuneva, Mariia, Beretta, Laura, DeBerardinis, Ralph J., Swinnen, Johannes V., Hodson, Leanne, Cassiman, David, Verslype, Chris, Christian, Sven, Grünewald, Sylvia, Grünewald, Thomas G. P., Fendt, Sarah-Maria·2019·Nature

Abstract

Most tumours have an aberrantly activated lipid metabolism1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers. In several human and mouse cancer cell lines and carcinomas, a sapienate biosynthesis pathway underpins metabolic plasticity by allowing these cells to bypass stearoyl-CoA desaturase-dependent fatty acid desaturation.

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Metadata

Authors
Vriens, K., Christen, S., Parik, S., Broekaert, D., Yoshinaga, K., Talebi, A., Dehairs, J., Escalona-Noguero, C., Schmieder, R., Cornfield, T., Charlton, C., Romero-Pérez, L., Rossi, M., Rinaldi, G., Orth, M. F., Boon, R., Kerstens, A., Kwan, S. Y., Faubert, B., Méndez-Lucas, A., Kopitz, C. C., Chen, T., Fernandez-Garcia, J., Duarte, J. A. G., Schmitz, A. A., Steigemann, P., Najimi, M., Hägebarth, A., Van Ginderachter, J. A., Sokal, E., Gotoh, N., Wong, K.-K., Verfaillie, C., Derua, R., Munck, S., Yuneva, M., Beretta, L., DeBerardinis, R. J., Swinnen, J. V., Hodson, L., Cassiman, D., Verslype, C., Christian, S., Grünewald, S., Grünewald, T. G. P., & Fendt, S.-M.
Venue
Nature
Published
2019-02-06
Volume
566
Issue
7744
Pages
403-406
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2913095286
Cited by
477
References
24
FWCI
16.66
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity. https://app.cochat.ai/papers/10.1038/s41586-019-0904-1
The paper
Vriens, K., Christen, S., Parik, S., Broekaert, D., Yoshinaga, K., Talebi, A., Dehairs, J., Escalona-Noguero, C., Schmieder, R., Cornfield, T., Charlton, C., Romero-Pérez, L., Rossi, M., Rinaldi, G., Orth, M. F., Boon, R., Kerstens, A., Kwan, S. Y., Faubert, B., . . . Fendt, S.-M. (2019). Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity. Nature. https://doi.org/10.1038/s41586-019-0904-1

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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