TAMPA, Fla. – Cells need energy to survive and thrive. In general, if oxygen is available, cells oxidize glucose to carbon dioxide, which is very effective, similar to burning gasoline in your car. However, even in the presence of adequate oxygen, many malignant cells choose instead to transfer glucose to lactic acid, a process that is much less efficient. This metabolic change is referred to as the Warburg Effect, as first described by Otto Warburg nearly a century ago. Ever since then, the conditions that would gradually select for cells to exhibit the Warburg Effect have been debated, as it is much less efficient and produces toxic waste products.
“The Warburg Effect is misunderstood because it doesn’t make sense for a cell to ferment glucose when it would get a lot more energy by oxidizing it. Our current study goes to the heart of the This problem with explaining the microenvironmental conditions in early cancers would be a preference for the Warburg phenotype.This is important because such cells are much more aggressive and more likely to lead to lethal cancers. , ”said Mehdi Damaghi, Ph.D., first author study and research scientist in the Department of Cancer Psychology at the Moffitt Cancer Center.
To better understand the selection conditions for the Warburg Effect and the mechanisms by which cells can induce this metabolic change, Moffitt researchers added undifferentiated cells to the microstructure of the tumor tumor. present at the time of early carcinogenesis, known as ductal carcinoma in situ (DCIS). DCIS is an unregulated growth of cells within the breast ducts. This is the earliest stage at which breast cancer can be diagnosed. Although considered noninvasive, it can cause invasive cancer in a fraction of cases. In a new research article published in the Proceedings of the National Academy of Sciences, Moffitt ‘s team shows that these conditions select cells to express the Warburg Effect.
The researchers hypothesized that the complex interaction of factors in hard tumor microenvironment within DCIS, such as low nutrition, low oxygen and high acidity, could pre-malignant cells exposing the Warburg phenotype to survive and thrive within these hostile conditions. To test their theory, the research team placed low glycolytic breast cancer cells under the various microenvironmental selection pressures (low oxygen, high acidity, low glucose and hunger) over 12 to 18 months. Following this selection, individual clones of the cancer cells were isolated and identified for their metabolic and transcriptomic profiles.
Their results indicate that the adverse metabolic conditions in the microenvironment of DCIS tumors induce these pre-malignant cells to select for the Warburg phenotype through transcription reprogramming. In particular, the researchers found that the activity and stability of the transcription factor, KLF4, allowed cancer cells to convert to a phenotype that survives in the harsh environment. “While it is clear that KLF4 is responsible for this phenotype in this particular system, we expect different cell lines to come up with their own approaches to address this need. for metabolic change. This is the ‘equality of action’ we have, “said Robert Gillies, Ph. D., senior author and chair of the Department of Cancer Psychology.” We have clearly shown that the phenotype this is selected by the harsh conditions of micro-environment. “
###
This research was supported by the National Cancer Institute (U54CA193489, U01CA232382, R01CA077575, P30-CA076292) and the Moffitt Center of Excellence for Evolutionary Medicine.
About Moffitt Cancer Center
Moffitt is specifically for one life-saving mission: contributing to cancer prevention and treatment. The Tampa-based facility is one of only 51 Comprehensive Cancer Centers designated by the National Cancer Institute, a distinction that recognizes Moffitt’s scientific excellence, multidisciplinary research, and robust training and education. Moffitt is the No. 11 cancer hospital and has been ranked nationally by U.S. News & World Report since 1999. Moffitt’s experienced nursing staff is recognized by the Magnet®-certified American Nurses Certification Center, the highest reputation. With more than 7,000 team members, Moffitt has an economic impact of $ 2.4 billion in the state. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the trend on Facebook, Twitter, Instagram and YouTube.
Disclaimer: AAAS and EurekAlert! they are not responsible for the accuracy of press releases posted to EurekAlert! by sending institutions or for using any information through the EurekAlert system.