PGK1 protein promotes brain tumor formation and cancer metabolism

March 03, 2016

PGK1, a glycolytic enzyme, has been found to play a role in coordinating cellular processes crucial to cancer metabolism and brain tumor formation, according to results published in today's online issue of Molecular Cell. The findings may lay the groundwork for improved approaches to diagnosis and treatment of glioblastoma and other cancers.

The study, led by The University of Texas MD Anderson Cancer Center, showed that PGK1, which is associated with tumor metastasis and drug resistance, was instrumental in glycolysis and the citric acid cycle, both important for generating the energy that feeds cancer cells. The paper sheds further light on the Warburg effect, an enzymatic pathway that cancer cells employ to boost energy levels and produce cellular substances that lead to rapid cancer growth.

"The Warburg effect promotes tumor progression. Exactly how this is coordinated has remained elusive," said Zhimin Lu, M.D., Ph.D., professor of Neuro-Oncology. "Our study highlights that PGK1 acts as a protein kinase in coordinating glycolysis and the citric acid cycle in cancer metabolism and tumor formation."

Normal cells generate oxygen for survival via a relatively low rate of glycolysis, which converts glucose into the enzyme pyruvate. Pyruvate is used in the citric acid cycle (TCA), a series of chemical reactions that generate energy.

Cancer cells however produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cell, a process that converts glucose into cellular energy and forms lactic acid. Normal healthy cells will bypass this fermentation process if oxygen is available. Malignant, rapidly growing tumors can experience glycolytic rates up to 200 times higher than those of healthy cells and will undergo lactic acid fermentation even in the presence of high oxygen levels.

"The Warburg effect is characterized by increased levels of glucose, lactate production and suppression of pyruvate metabolism in mitochondria," said Lu. "Exactly how this process is coordinated with cancer metabolism has been little understood."

Lu's team found that a cellular chain of events involving activation of cancer genes like EGFR, KRAS and B-Raf and the protein ERK, allowed PGK1 to "translocate" into the cell's mitochondria. Mitochondria are membrane-containing cell components crucial for producing energy. 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.

"Our findings provided critical insight into the Warburg effect and demonstrates that PGK1 ultimately promotes cancer cell proliferation and tumor formation," said Lu. "It may help us to develop a molecular basis for improved diagnosis and treatment of cancer."
-end-
MD Anderson team participants included Xinjian Li, Ph.D., Yuhui Jiang, Ph.D., Weiwei Yang, Ph.D., Yanhua Zheng, Ph.D. and Yan Xia, Ph.D., all of Neuro-Oncology; and David Hawke, Ph.D. and Kenneth Aldape, M.D., Pathology. Other participating institutions included Shanghai Jiaotong University, China, and the Salk Institute for Biological Studies, La Jolla, Calif.

The study was funded by the National Institutes of Health (2R01 CA10935, 1R0CA169603, 2P50CA127001, 1R01NS089754, CA16672, and CA82683).

University of Texas M. D. Anderson Cancer Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.