A new study identifies an unexpected molecular link between liver cancer, cellular stress, and risk factors for developing this cancer – obesity, alcoholism, and viral hepatitis. In the study by University of Iowa researchers and published in the journal PLOS Genetics, researchers show that a protein called CHOP, which had previously been thought to generally protect against cancer, actually promotes liver cancer in mice.
Obesity, alcoholism, and chronic hepatitis all increase the risk of getting liver cancer, the third leading cause of cancer death worldwide. There are few good treatment options for advanced liver cancer and rates of the disease have doubled in the U.S. in the past 20 years, driven in part by increasing obesity.
Obesity, alcoholism, and viral hepatitis also cause cellular stress and induce expression of CHOP, a transcription factor that is known to promote cell death. The study shows that in mice, despite its role in cell death, CHOP is actually elevated in cancerous liver cells. Furthermore, mice without CHOP are partially protected from liver cancer, developing fewer and smaller tumors than the normal mice in response to liver cancer-causing drugs. Tissue samples from human patients show that CHOP is also elevated in human liver tumors compared to surrounding non-tumor tissue from the same patients.
Having implicated CHOP as a contributing factor in liver cancer associated with obesity, alcoholism, and hepatitis, the UI team plans to identify the other proteins that partner with CHOP to promote liver cancer. A better understanding of this biological pathway may lead to targets for therapies to better treat liver cancer.
Journal
PLoS Genetics