【PNAS】Northwestern University research found that lipid balance - a key factor regulating cancer cell metastasis and survival

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Written by Sophia

Fatty acids are an important source of energy and a key component of
phospholipids in membranes and organelles.
Saturated fatty acids (SFA) are converted to unsaturated fatty acids (UFA) by stearoyl CoA desaturated enzyme (SCD), an enzyme
that is active in cancer.

Northwestern researchers have found that this particular enzyme is essential for regulating cancer cell survival and metastasis under cellular stress, and the findings, published in the Proceedings of the National Academy of Sciences, titled "Ovarian cancer cell fate regulation by the dynamics between saturated and.
" unsaturated fatty acids”
。 Daniela Matei suggests that combining this enzyme with dietary interventions could be a promising treatment strategy
for cancer.

style="box-sizing: border-box;" _msthash="251139" _msttexthash="381004">Research background

 01 

When glucose and oxygen are confined in the tumor microenvironment, fatty acids or lipids can be used as alternative energy sources
for cancer cells.
To maintain proper intracellular function, including cell signaling and lipid storage, saturated fatty acids are converted to unsaturated fatty acids
through an enzyme called stearoyl CoA desaturated enzyme (SCD).
This "desaturation" is the final step in fat production, the process
of converting metabolites into fatty acids and energy.

While SCD is well known to be essential for maintaining lipid balance in cancer cells, how it affects cancer cell survival and tumor progression is still poorly
understood.
Previous work in the Matei lab confirmed that cancer stem cells are rich in unsaturated fatty acids, and targeting SCD can eliminate cancer stem cells
.

Research progress

 02

During the study, researchers used transcriptomics, lipidomics, and single-cell imaging to reveal how SCD regulation of fatty acids affects ovarian cancer cell survival
.
Increased lipid unsaturation levels facilitated by SCD protect cancer cells from endoplasmic reticulum stress-induced apoptosis
.
Reduced levels of unsaturated fats caused by SCD depletion or SCD inhibition and a diet rich in saturated fats can stop cancer cell growth in vitro and tumor progression
in vivo.

Studies have found that inhibition or elimination of SCD can completely reduce the amount of unsaturated fatty acids in cancer cells, tilting the balance in
favor of saturated fatty acids.
In contrast, increased levels of unsaturated fatty acids protect cancer cells from cellular stress triggered by the endoplasmic reticulum (ER), a network of tubules in the cytoplasm that transports proteins and lipids
throughout the cell.

"The balance between saturated and unsaturated fatty acids is important
to maintain the integrity of the endoplasmic reticulum," says Matini.
Therefore, if there are too many saturated fatty acids, the cells die, but unsaturated fatty acids act like buffers
.
”

Next, using an ovarian cancer xenograft model, the researchers found that inhibition of SCD could stop tumor growth
in the body.
The depletion of SCD leads to a decrease in the level of UFA and SFA and alters the plasticity
of fatty acyl chains.
In addition, in an in vivo model of ovarian cancer, a combination intervention using SCD inhibitors and an SFA-rich diet triggered ER stress in tumors growing in vivo and effectively stopped the spread
of cancer cells.

Research implications

 03 

The results suggest that SCD is 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 have largely hampered previous attempts to use metabolic interventions to target cancer, the findings underscore the importance of
a combined strategy.

Resources:

https://medicalxpress.
com/news/2022-10-role-fatty-acids-cancer-cell.
html

style="white-space: normal;box-sizing: border-box;" _msthash="251155" _msttexthash="19521346">Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.