Nine Year Study Finally Explains The Relationship Between Sugar And Cancer
Scientists have discovered the exact relationship between sugar and cancer by revealing that the way in which cancer cells break down sugar is linked to the stimulation of tumor growth.
Cancer cells tend to produce energy differently from normal cells – they use a process that involves fermentation of glucose into lactate, rather than ordinary respiration.
Every cell in the body needs sugar to survive. But cancer cells seem to require more than healthy cells do. They also seem to break sugar down faster. Cancer’s mechanism of speedily metabolizing sugar is known as the Warburg effect.
Scientists have long pondered whether this phenomenon is related to how aggressively tumors grow.
"Our research reveals how the hyperactive sugar consumption of cancerous cells leads to a vicious cycle of continued stimulation of cancer development and growth,” explained study author Professor Johan Thevelein, from Belgium’s VIB-KU Leuven Center for Cancer Biology, in a statement.
“Thus, it is able to explain the correlation between the strength of the Warburg effect and tumor aggressiveness. This link between sugar and cancer has sweeping consequences. Our results provide a foundation for future research in this domain, which can now be performed with a much more precise and relevant focus."
Before now it wasn’t clear whether the Warburg effect was just a symptom of cancer, or whether it could affect tumor growth. The new study shows that the Warburg effect actually stimulates the growth of cancerous tumors – although this in no way means that sugar causes cancer. The findings are published in the journal Nature Communications. . . .
Research reveals what the Warburg pathway can do for breast cancer growth
To generate energy from glucose, cells can use one of two pathways. One of them takes place in the mitochondria, energy-producing structures inside cells, and yields significantly more energy – ATP – than the second pathway, called fermentation. Normal cells mostly use the path in the mitochondria, but about 80 percent of cancer cells seem to have revamped their metabolism to preferentially generate energy via fermentation. This phenomenon is known as the Warburg effect.
“In the 1920s, Otto Warburg and his colleagues discovered that cancer cells consume larger amounts of glucose than normal cells, and most cancer cells process it via fermentation,” said senior author Dr. Bert O’Malley, chair and professor of molecular and cellular biology, Thomas C. Thompson Chair in Cell Biology and associate director of basic research in the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.
The Warburg effect has been a mystery for quite some time. Why would cancer cells, which need large amounts of energy to sustain their growth, prefer to use a pathway that produces less ATP than another available pathway? What would be the advantage for cancer cells to use the Warburg pathway? This study sheds new light on this mystery.
The Warburg pathway – cancer connection
The O’Malley laboratory identified years ago SRC-3, a protein that is an important regulator of gene expression. SRC-3 is overproduced in most cancer cells and this transforms it into an oncogene; it can turn on genes involved in abnormal growth, invasion, metastasis and resistance to anti-cancer drugs. If cancer cells modify SRC-3, for example by adding a phosphate chemical group to it, then SRC-3 becomes hyperactive, a hallmark of many tumors.
“We conducted an unbiased search to identify enzymes that add phosphate groups that are able to enhance the activity of SRC-3,” said first author Dr. Subhamoy Dasgupta, who was a trainee and junior faculty while he was working on this project in the O’Malley lab and is currently an assistant professor of cell stress biology at Roswell Park Comprehensive Cancer Center.
“We were surprised to identify an enzyme named PFKFB4 as one of the most dominant regulators of protein SRC-3. This was unexpected because PFKFB4 was well known for its ability to only add phosphate groups to sugars in the Warburg pathway. Nobody had described before that this enzyme could also add phosphate groups to proteins,” Dasgupta said.
“When PFKFB4 adds a phosphate group to SRC-3, it transforms it into a potent driver of breast cancer and other cancers as well,” O’Malley said.
“I am most excited about our findings regarding breast tumor progression in mouse models,” said Dasgupta. “Our data shows that by removing PFKFB4 or SRC-3 from the tumors, we are able to almost completely eliminate recurrence and metastasis of breast cancer. In addition, modification of SRC-3, so it cannot receive a phosphate group, also results in tumor control.”
These and other findings allowed the researchers to connect for the first time the Warburg pathway to cancer growth. PFKFB4, an enzyme involved in the Warburg pathway, also is able to modify SRC-3, a potent driver of cancer growth. Absence of PFKFB4 or SRC-3, or the presence of an SRC-3 form that cannot be modified by PFKFB4, eliminates recurrence and metastasis.
1.1. The Warburg effect stimulates the growth of
cancerous tumor. This does not mean that sugar causes cancer. 2.SRC-3 is a protein and important regulator of
gene expression. SRC-3 is overproduced in most cancer cells. SRC-3 can turn on genes involved in abnormal
growth, invasion, metastasis and resistance to anti-cancer drugs. 3. PFKFB4, an enzyme, is one of the most dominant
regulators of protein SRC-3. 4.When PFKFB4 adds a
phosphate group to SRC-3, it transforms it into a potent driver of breast
cancer and other cancers. 5.By removing PFKFB4 or
SRC-3 from the tumors, the study was able to almost completely eliminate
recurrence and metastasis of breast cancer. 6. A modification
of SRC-3, so it cannot receive a phosphate group, also results in tumor
control. 7.Absence of PFKFB4 or SRC-3, or the presence of
an SRC-3 form that cannot be modified by PFKFB4, eliminates recurrence and
metastasis. 8.These findings give researchers additional
intervention points for future therapies to target PFKFB4 or SRC-3. 9.Hopefully this will result in clinical trials
with humans and potentially become targeted therapy sometime in the future.
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09) 11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15
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