PNAS: uncovering the important role of key enzymes in cancer cell survival and metastasis

Scientists from Northwestern University and other institutions have found that under cellular stress, a special enzyme is important
for regulating cancer cell survival and metastasis.

Fatty acids are an important source of energy and a key component of phospholipids in cell membranes and organelles, saturated fatty acids (SFAs) can be converted into unsaturated fatty acids (UFAs)
by stearoyl CoA desaturated enzyme (SCD), an active enzyme in cancer.

Recently, a research report entitled "Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids" was published in the international journal Proceedings of the National Academy of Sciences.
Scientists from Northwestern University and other institutions have found that a special enzyme is important for regulating cancer cell survival and metastasis in a state of cellular stress, and the results suggest that targeting this enzyme in combination with dietary interventions may be a promising potential strategy
for the treatment of cancer.

When glucose and oxygen are confined in the tumor microenvironment, fatty acids, or fats, can be used as alternative energy sources for cancer cells, and in order to maintain normal intracellular functions (including cell signaling and lipid storage), saturated fatty acids are converted into unsaturated fatty acids through SCD enzymes, and this "desaturation" is the final step in fat production, that is, the process
of converting metabolites into fatty acids and energy 。 Although scientists know that SCD enzymes are important for maintaining lipid balance in cancer cells, they do not know how they affect cancer cell survival and tumor progression; However, researchers have previously found that cancer stem cells are rich in unsaturated fatty acids, and targeting SCD enzymes can eliminate cancer stem cells
.

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In the current study, the researchers used transcriptomics, lipidomics, and single-cell imaging techniques to reveal how SCD's regulation of fatty acids affects ovarian cancer cell survival
.
It was found that inhibition or elimination of SCD could reduce the level of unsaturated fatty acids in cancer cells and tilt the balance towards saturated fatty acids.
In contrast, increasing levels of unsaturated fatty acids may protect cancer cells from cellular stress induced by the endoplasmic reticulum, a reticular structure in the cytoplasm that helps transport proteins and lipids
throughout the cell.

Researcher Matei said that the balance between saturated and unsaturated fatty acids is important to maintain the integrity of the intraplasmic reticulum in cells, so if too many saturated fatty acids are present, cells will die; But unsaturated fatty acids act as a kind of buffer; Subsequently, after studying the ovarian cancer xenograft model, the researchers found that inhibiting the function of SCD may block tumor growth in vivo, and in vivo models of ovarian cancer, combining SCD inhibitors with a diet rich in saturated fatty acids may turn on the endoplasmic reticulum stress response and block tumor progression
.
This study reveals that SCD may be a key regulator of cancer cell fate under metabolic stress, and targeting lipid balance in cancer cells may be an effective therapeutic strategy
.

Given the plasticity and redundancy of metabolic pathways, which largely thwart scientists' attempts and ideas to use metabolic interventions to target cancer, the results of this study highlight the importance of
a combinatorial strategy.
In summary, the results of this study suggest that SCD enzymes may act as a key regulator of cancer cell fate under metabolic stress conditions, and point out potential therapeutic strategies
that target lipid balance.
(Bio Valley Bioon.
com)

Original source:

Guangyuan Zhao, Yuying Tan, Horacio Cardenas, et al.
Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids, Proceedings of the National Academy of Sciences (2022).
DOI: 10.
1073/pnas.
2203480119