Liver cancer cells stop making glucose as they become cancerous

July 30, 2012

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 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 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 .

The research is published in the journal Hepatology.

"This study identifies an important mechanism that severely blocks and its release from the liver as 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.

Explore further: miR-122: Loss of tiny liver molecule might lead to liver cancer

Related Stories

Anti-sense might make sense for treating liver cancer

January 3, 2012

A new study shows that it is possible to selectively target and block a particular microRNA that is important in liver cancer. The findings might offer a new therapy for this malignancy, which kills an estimated 549,000 people ...

Recommended for you

Dogs detect breast cancer from bandage: researchers

March 24, 2017

Dogs can sniff out cancer from a piece of cloth which had touched the breast of a woman with a tumour, researchers said Friday, announcing the results of an unusual, but promising, diagnostic trial.

'Jumonji' protein key to Ewing's sarcoma rampage

March 24, 2017

By the time Ewing's Sarcoma is diagnosed, primarily in teens and young adults, it has often spread from its primary site to other parts of the body, making it difficult to treat. A University of Colorado Cancer Center study ...

In a sample of blood, researchers probe for cancer clues

March 24, 2017

One day, patients may be able to monitor their body's response to cancer therapy just by having their blood drawn. A new study, led by bioengineers at UC Berkeley, has taken an important step in that direction by measuring ...

Researchers gain insight into breast cancer drug resistance

March 24, 2017

Breast cancer's ability to develop resistance to treatment has frustrated researchers and physicians and has thwarted even the latest and greatest targeted therapies. For example, after researchers identified a disease pathway ...

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.