PGK1 protein promotes brain tumor formation and cancer metabolism

March 3, 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 cycle, both important for generating the energy that feeds . 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 and ."

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 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 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."

Explore further: Novel regulatory mechanism for cell division found

Related Stories

Novel regulatory mechanism for cell division found

November 21, 2014
A protein kinase or enzyme known as PKM2 has proven to control cell division, potentially providing a molecular basis for tumor diagnosis and treatment.

Link between colon cancer and metabolism identified

May 13, 2014
More than 60 years ago Otto Warburg recognized that cancer cells differ from normal cells in the metabolic pathway they use for the oxidation of sugar. Rather than the typical series of oxidative steps that take place in ...

Study reveals new insight into DNA repair

August 3, 2015
DNA double-strand breaks (DSBs) are the worst possible form of genetic malfunction that can cause cancer and resistance to therapy. New information published this week reveals more about why this occurs and how these breaks ...

Metabolic protein launches sugar feast that nurtures brain tumors

November 26, 2012
Researchers at The University of Texas MD Anderson Cancer Center have tracked down a cancer-promoting protein's pathway into the cell nucleus and discovered how, once there, it fires up a glucose metabolism pathway on which ...

Researchers uncover signal that switches cells to cancerous metabolism

February 11, 2015
Abnormal metabolism within the cells is a distinctive characteristic of cancer, but until now, the mechanism that causes cells to undergo this metabolic shift remained unknown.

Protein controlling glucose metabolism also a tumor suppressor

December 6, 2012
A protein known to regulate how cells process glucose also appears to be a tumor suppressor, adding to the potential that therapies directed at cellular metabolism may help suppress tumor growth. In their report in the Dec. ...

Recommended for you

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.