OCT 31, 2019 7:43 PM PDT

Unpacking lactate's role in the Warburg effect

In a recent issue of Nature, the findings of one study made a particularly big splash: how and why cancer cells use energy differently than healthy cells. The research builds on an already well-establish field in cancer that is known as the Warburg effect, named after German physiologist and physician Otto Warburg. The phenomenon refers to the specific way that cancer cells consume energy – i.e. through glycolysis instead of through oxidative phosphorylation, which is the process that healthy cells undergo. While Warburg explained this effect nearly 90 years ago, the field of cellular metabolism still lacks much in the way of comprehension. This study, conducted by scientists at the University of Chicago, aimed to clear up some of the unanswered questions surrounding the topic.

Scientists have been trying to figure out the inner-workings of cellular metabolism and the Warburg effect for years. Photo: Pixabay

"What makes the Warburg effect so interesting to study is that it's an important and common cancer phenomenon, but no one ever understood if this process has regulatory functions on diverse types of cells in a tumor, and how," explained lead author Yingming Zhao, PhD, who is a professor in the Ben May Department for Cancer Research. "As a technologist and biochemist, I enjoy figuring out how we can answer exciting questions like this and figure out details."

Using mass spectrometry, Zhao and colleague Lev Becker, PhD, figured out that lactate, which is the end product of the Warburg effect and has been shown to play a role in regulatory functions in immune and stem cells, has another non-metabolic function – mainly, it produces and stimulates histone lactylation, a new kind of histone modification.

In this modification, histone lactylation changes structural DNA units in cells, thus altering the combination of genes expressed and functions of macrophages from a pro-inflammatory and anti-bacterial state (M1) to an anti-inflammatory and reparative state (M2). While this may sound beneficial, previous studies have determined that while the reparative M2 state is conducive to curbing bacterial infections, it actually encourages the growth, metastasis and immune suppression of cancer tumors. The scientists’ findings confirmed this same phenomenon with the occurrence of histone lactylation, showing that elevated lactate and histone lactylation levels in macrophages could play a factor in the formation and development of tumors.

"That a single metabolite can have such a powerful effect on immune cell function is both remarkable and surprising," Becker said. "Our discovery of histone lactylation and its impact on macrophage biology serves as a blueprint to understand how lactate alters other cell types and unravel the mysteries of the Warburg effect and its impact on human disease."

Due to the fact that the Warburg effect is present in the majority of cancers, as well as many autoimmune diseases, atherosclerosis, diabetes and aging, the researchers hope that their findings will light the way to the development of new drugs that are capable of specifically targeting this phenomenon.

Sources: Nature, Science Daily

About the Author
  • Kathryn is a curious world-traveller interested in the intersection between nature, culture, history, and people. She has worked for environmental education non-profits and is a Spanish/English interpreter.
You May Also Like
MAR 11, 2021
Cell & Molecular Biology
Deadly Cancer Cells Can Move in the Wrong Direction
MAR 11, 2021
Deadly Cancer Cells Can Move in the Wrong Direction
Cancer is most deadly when it metastasizes; when cells break away from a primary site of cancer and move through the bod ...
MAR 12, 2021
Cancer
Toxic molecules in flame retardants increase breast cancer risk
MAR 12, 2021
Toxic molecules in flame retardants increase breast cancer risk
New research reported in the February issue of the journal Toxicological Sciences suggests that brominated flame re ...
MAR 24, 2021
Cancer
What toxic chemicals are lurking in your couch?
MAR 24, 2021
What toxic chemicals are lurking in your couch?
New research published in the journal Environment International suggests a weekend trip to the nearest furniture st ...
APR 07, 2021
Cancer
Does inhibiting NLRP3 inhibit melanoma tumor growth?
APR 07, 2021
Does inhibiting NLRP3 inhibit melanoma tumor growth?
Researchers at the University of Colorado Cancer Center have published exciting findings in the Proceedings of the Natio ...
APR 09, 2021
Cancer
Employing machine-learning to identify the biological languages of cancer and Alzheimer's
APR 09, 2021
Employing machine-learning to identify the biological languages of cancer and Alzheimer's
In a study published in the scientific journal PNAS, researchers from St. John's College and the  University of ...
JUN 04, 2021
Cancer
Cancer patients with COVID-19 fare better with remote health monitoring
JUN 04, 2021
Cancer patients with COVID-19 fare better with remote health monitoring
A new study presented last week at the American Society of Clinical Oncology Annual Meeting after its publication in the ...
Loading Comments...