Dallas (TCA/DPA) – Fat is not just a guilty pleasure – this is the secret weapon of cancer. New research from the Southwestern Medical Center UT sheds light why this is the case.
In a study published this month in the journal Nature, researchers found cancer cells to steal fat molecules from the blood, arming themselves with a powerful antioxidant that protects them from death.
Tumors seem to do this by moving in lipoproteins-molecules that carry fat and fat-soluble nutrients such as vitamin E in the blood-through molecules covered with sugar on their cell surface. These sulfateted glycosaminoglycans (or GAGS) allow cancer cells to strengthen their cell membranes with vitamin E and avoid a form of cell death called ferroptosis.
Although clinical applications are still excluded, the study emphasizes how to understand the metabolism of cancer can open new doors for treatment, said Dr. Shad Taxon, Assistant Professor of Urology at Northwestern University of Fayinberg Medical School who did not participate in the study.
“I think this document and others in the field (emphasize) the assessment of ferroptosis as a mechanism for killing cancer cells – that the mechanism of cell death is so intimately intertwined with cellular metabolism,” Taxon said. “I think what is interesting to humans is that metabolism has a really major impact on the potential vulnerability of cancer cells to specific therapies.”
Construction blocks with functional advantages
Cancer diseases redirect their metabolism in ways that support their growing horde of destructive cells. Part of this rewind involves the production of glucose energy and the acquisition of cellular building blocks such as nucleic acids, proteins and lipids.
Amassing Cellular Building Blocks is Especially Crucial Since A Tumour’s Uncontrolled Growth Lends to It Creating A Hosile Microenvironment There Arente Enghh Nut Garcia-Bermudez, An Assistant Professor at Ut Southwestern Medical Center’s Children’s Medical Center Research Institute, Who Led The Study.
Lipids are essential for tumor growth and progression. The plasma membrane of each cell is two -layer lipids; Because cancer cells swell in number, they must deplete lipids from their immediate environment or make their own to maintain their plasma membranes.
Garcia-Bermudes said this is the prevailing theory of why lipids are so important to cancer. Since then, emerging studies have found that lipids can offer cancer cells more functional fins. For example, a September 2024 study found that cancer cells use lipids called sphingolipids to switch to stealth mode, avoiding detection and destruction by the immune system.
Studies have also found that lipids are involved in ferroptosis, a type of cell death discovered in 2012. Portmanmato of “iron”, the Latin word for iron, and apoptosis, the scientific word for programmed cell death
“Oxidants damage the lipids that form the membranes (on) cell,” said Garcia-Bermudes. “The interesting thing is that cancer cells tend to produce more oxidants than normal cells,” he added, noting that he has an interest in understanding why some cancers are more susceptible to this type of damage and the use of ferroptosis to kill cancer cells.
Cut BlundersKill the Cancer
The cunning masters of survival as they are, cancer cells have come up with ways to avoid ferroptosis. Unraveling the reason why you put a Garmwood Garmudez and his laboratory on a four-year scientific study.
One of the first discoveries of the researchers, after screening 200 metabolic genes associated with cancer, is that an enzyme called glutathione peroxidase 4 is active in tumors. This was not a new discovery: studies show that this enzyme, which can stop lipids from degradation, play a major role in controlling ferroptosis.
When glutathionic peroxidase 4 is deleted from the cancer cell genome, the tumor will die – unless it is administered medicine that blocks ferroptosis or fed lipoproteins.
“It was the clue that lipoproteins were somehow associated with ferroptosis,” says Dr. Ralph Debbardis, Director of the Center for Human Growth and Development of the Southwestern Medical Center of UT, which co -author of the study.
In a battery of experiments involving cancer cell deprivation in lipoproteins and exposure to various antioxidants, the full picture began to reveal itself. Cancer cells capture lipoproteins, especially those that carry vitamin E-fat soluble antioxidant from their surroundings. Like a fisherman with a fishing line, the cancer cells achieved this not with the usual drums used to capture lipoproteins, but with long, flowing sugar chains called sulfate glycosaminoglycans (or GAGS). These molecules are attached to the surface of the cancer cells through another molecule called Proteoglycan.
When scientists blocked the biochemical path responsible for the production of GAG, this limited the access of the cancer cell grown in the laboratory to Vitamin E and made it more vulnerable to ferroptosis. In mice grafted with cancer cells, cutting the road slowed the growth of the tumor.
Researchers also examined 20 tumors donated by patients with clear cellular kidney carcinoma, the most common type of kidney cancer affecting over 640,000 people in the United States. These tumors have higher levels of GAGS and Vitamin E – about 15 times more than the latter – compared to normal kidney tissue. The interruption of the biochemical pathway producing bluffs prevents kidney cancer cells from absorbing lipoproteins with vitamin E dying from the iron hand of ferroptosis.
Future research
Garcia-Bermudes and Debiandis warn that much more studies need to be done before the discoveries of their study have a clinical application for the treatment of cancer.
“We know that the bluffs are on the surface, they talk to lipoproteins and affect the absorption of lipoproteins,” said Garmia-Bermudes. “But how mechanically it happens, especially in the cancer cell, it is not shown before… If we understand how it works and we find molecular goals that we can treat with medicines and blocking, then we have a way to exhaust vitamin E in the tumor.”
Deberardinis said the study does not imply a link between dietary vitamin E and the risk of cancer or how vitamin E levels correlate with the results of the cancer patient. Inventing these possible relationships would be points for a future study.
In the short term, said Deberardinis, these discoveries can be used to study whether tumors with higher levels of glycosaminoglycans or stored vitamin E are related to the patient’s results, such as the percentage of survival or how well they respond to treatment.
Taxon said there are no federally approved cancer treatments at the moment to encourage pheroptosis. His laboratory at the Medical School at the Northwestern University of Feinberg conducts research on synthetic lipoproteins, deprived of all lipid passengers – a Trojan horse, without soldiers hiding inside.
Cancer cells expect to get lipoproteins with fat like cholesterol and vitamin E, Taxon said, but “they eventually die of ferroptosis. Our medicine carries nothing and it is through this mechanism by which you can kill the cell.”
For Garcia-Bermudes and Debianardis, their research efforts were like finding a needle in hay, one in which they hoped to find more needles.
“Our study is really exciting, but at the same time it is a very main discovery,” said Garcia-Bermudes. “It was amazing to find something that people did not watch in cancer before, to understand why these tumors were so sustainable. I’m super excited to continue working on it.”