PGK1 Plays a Role in Brain Cancer Growth

A new study reveals clues on how brain tumors develop and spread, and this new information may provide valuable insight into diagnosis and treatment. 

Approximately 23,770 malignant tumors of the brain or spinal cord will be diagnosed annually, according to the American Cancer Society. How and why these tumors spread has been studied at great lengths, and new research appears to answer some of these complicated questions.

Researchers at The University of Texas MD Anderson Cancer Center, showed that PGK1 protein coordinates glycolysis-an energy conversion pathway-and the tricarboxylic acid (TCA) cycle, which plays a role in the development and growth of cancer in the brain. PGK1 is associated with tumor metastasis and drug resistance, and the team is working to learn more about how rapid cancer growth takes place at the cellular level. This study was just published in the journal Molecular Cell.

The study focused on a process known as the Warburg effect, which is a pathway that cancer cells use to boost energy levels and produce cellular substances that lead to rapid metastasis.

“The Warburg effect promotes tumor progression. Exactly how this is coordinated has remained elusive,” said Zhimin Lu, MD, PhD, professor of Neuro-Oncology at MD Anderson, in a news release. “Our study highlights that PGK1 acts as a protein kinase in coordinating glycolysis and the citric acid cycle in cancer metabolism and tumor formation.”

A cellular chain of events involving activation of cancer genes like EGFR, KRAS, BRAF, and the protein ERK, allowed PGK1 to translocate into the cell’s mitochondria, according to Dr. Lu. PGK1 acted as a protein kinase in mitochondria and activated a critical enzyme that inhibited the mitochondria’s ability to use pyruvate, suppressed chemically reactive molecules containing oxygen and increased lactate levels.

This work highlights that PGK1 acts as a protein kinase in coordinating glycolysis and the TCA cycle, which is instrumental in cancer metabolism and tumorigenesis.

More data on this research will be critical to save the lives of patients. As it stands, approximately 16,050 people will die from brain and spinal cord tumors this year.