Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Liver Cancer Cells Stop Making Glucose As They Become Cancerous

31.07.2012
Liver cells normally produce glucose to help maintain healthy blood-sugar levels, but they lose that ability when they become cancerous, this study shows.
This change might benefit tumor cells by helping them grow and proliferate.
The study tracks how this loss happens and suggests that reversing it might offer a new way to treat this often-deadly disease.
COLUMBUS, Ohio – As liver cancer develops, tumor cells lose the ability to produce and release glucose into the bloodstream, a key function of healthy liver cells for maintaining needed blood-sugar levels.

The findings come from a study by scientists at The Ohio State Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

The loss of this type of glucose production, a process called gluconeogenesis, is caused by the over-expression of a molecule called microRNA-23a. The change might aid cancer-cell growth and proliferation by helping to maintain high levels of glycolysis under conditions of drastically reduced mitochondrial respiration, also known as the Warburg effect.

The findings suggest that suppressing miR-23a might reverse this process and offer a new treatment for hepatocellular carcinoma (HCC), the most common form of liver cancer.

The research is published in the journal Hepatology.

“This study identifies an important mechanism that severely blocks glucose production and its release from the liver as liver cells transform into cancer cells,” says principal investigator Dr. Samson Jacob, professor of molecular and cellular biochemistry and William and Joan Davis Professor in Cancer Research, Division of Hematology and Oncology at Ohio State and co-leader of the OSUCCC – James Experimental Therapeutics Program. “It is conceivable that delivery of an anti-miR23a to the tumor site could reverse this.”

For this study, Jacob and his colleagues used an animal model that develops diet-induced HCC, along with primary-tumor samples from patients and HCC cell lines. The mouse model mimics different stages of human hepatocarcinogenesis. Key findings include:

Levels of enzymes in the gluconeogenesis pathway were drastically reduced, along with transcription factors involved in the expression of the genes encoding those enzymes.

miR-23a expression was significantly up-regulated in the animal model and in primary human HCC.

miR-23a suppresses the enzyme glucose-6-phosphatase and the transcription factor PGC-1a, two important components of the gluconeogenesis pathway.

Interleukin-6 and Stat-3 signaling cause the upregulation of miR-23a.

“Based on our data,” Jacob says, “we conclude that gluconeogenesis is severely compromised in HCC by IL6-Stat3-mediated activation of miR-23a, which directly targets and suppresses glucose-6-phosphatase and PGC-1a, leading to decreased glucose production in HCC.”

Jacob notes that since glucose-6-phosphatase is also essential for liver cells to convert glycogen (the storage form of glucose) to glucose, suppression of this enzyme can block all pathways leading to glucose production by the liver.

Funding from the NIH/National Cancer Institute (grants CA086978) and NIH/National Institute of Diabetes and Digestive and Kidney Diseases (grant DK088076) supported this research.

Other Ohio State researchers involved in this study were Bo Wang, Shu-Hao Hsu, Wendy Frankel and Kalpana Ghoshal.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State’s cancer program as “exceptional,” the highest rating given by NCI survey teams. As the cancer program’s 210-bed adult patient-care component, The James is a “Top Hospital” as named by the Leapfrog Group and one of the top 20 cancer hospitals in the nation as ranked by
U.S.News & World Report.

Contact: Darrell E. Ward, Medical Center Public Affairs and Media Relations,
614-293-3737, or Darrell.Ward@osumc.edu

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

More articles from Health and Medicine:

nachricht Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering

nachricht New discoveries predict ability to forecast dementia from single molecule
12.12.2018 | UT Southwestern Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>