Featured Research

from universities, journals, and other organizations

Liver cancer cells stop making glucose as they become cancerous

Date:
July 30, 2012
Source:
Ohio State University Medical Center
Summary:
Research has shown that as liver cancer develops, tumor cells lose the ability to produce and release glucose into the bloodstream. 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 reversing this process might offer a new treatment for the most common form of liver cancer.

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.

Related Articles


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 DK088076) supported this research.

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


Story Source:

The above story is based on materials provided by Ohio State University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bo Wang, Shu-Hao Hsu, Wendy Frankel, Kalpana Ghoshal, Samson T. Jacob. Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating Glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. Hepatology, 2012; 56 (1): 186 DOI: 10.1002/hep.25632

Cite This Page:

Ohio State University Medical Center. "Liver cancer cells stop making glucose as they become cancerous." ScienceDaily. ScienceDaily, 30 July 2012. <www.sciencedaily.com/releases/2012/07/120730141635.htm>.
Ohio State University Medical Center. (2012, July 30). Liver cancer cells stop making glucose as they become cancerous. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2012/07/120730141635.htm
Ohio State University Medical Center. "Liver cancer cells stop making glucose as they become cancerous." ScienceDaily. www.sciencedaily.com/releases/2012/07/120730141635.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins