New technology reveals that individual cancer cells have different appetites for fatty acids


Electron microscopic image of a single human lymphocyte. Credit: Dr. National Cancer Institute Knitwear

A new method developed by the Institute of Systems Biology (ISB) and the University of California, Riverside, provides new insights into the biology of cancer by allowing researchers to show how fatty acids are absorbed by individual cells.

Fatty acids along with glucose and , are an important source of energy for cell growth and proliferation, and abnormal fatty acid metabolism is often seen in cancer. The laboratory of Dr. Wei Wei at ISB and the laboratory of Dr. Min Xue at UC Riverside have been collaborating for years to develop a series of chemical probes and analytical approaches to quantify cells glucose uptake, lactate production, absorption of amino acids, and another cancer-related metabolites.

Unlike glucose and amino acids, however, the mechanisms underlying the uptake of fatty acids into cells have been less well known and difficult to discern. The technical tools for measuring the uptake of fatty acids at the level of a single cell are extremely limited.

“This work is the first example of fatty acid absorption profiles in conjunction with the signaling of aberrant proteins in cancer cells at single cell resolution and represents a major breakthrough in the metabolic assay of a single cell, ”said ISB Assistant Professor Dr. Wei Wei, co-author of a newly published document in the Journal of the American Chemical Society.

To profile the uptake of fatty acids, the researchers chose a substitute molecule that was structurally similar to the natural one. . This resemblance tricked the cells into adopting these substitutes as the natives. Then, using a single dendrimer molecule, a tree-shaped polymer, the researchers achieved an accurate quantification of these dendrimer substitutes. .

Applying this new monocellular tool to a model of brain cancer, the researchers identified that fatty acid uptake was differentially regulated by two downstream effector targets of mammalian rapamycin (mTOR), a critical regulator of cell proliferation and protein synthesis. The results revealed a compensatory activation of fatty acid metabolism after oncogen inhibition or attenuation of glucose metabolism in these brains. and discovered a new combination therapy aimed at this bioenergetic flexibility to synergistically block tumor growth.

“This new tool opens up new avenues for studying the degree metabolism affects biological systems. It has also inspired us to develop more metabolic probes for single-cell analysis, ”said Riverside University associate professor Dr. Min Xue, the author of the paper.

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More information:
Zhili Guo et al, Monocellular fatty acid uptake profiles with surface-immobilized dendrimers, Journal of the American Chemical Society (2021). DOI: 10.1021 / jacs.1c05103

Provided by the Institute of Systems Biology

Citation: Add fatty acid to taste: new technology reveals that individual cancer cells have different appetites for fatty acids (2021, July 16) recovered on July 16, 2021 at -07-fatty-acid-technology- reveals-cancer.html

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