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Possible New Prognostic Marker and Therapeutic Target for Liver Cancer

Michael Karin, Ph.D.
University of California, San Diego
P42ES010337

High levels of the protein p62 in human liver samples are associated with cancer recurrence and reduced patient survival, according to a new study by NIEHS-funded researchers. The researchers also found that p62, a protein known to recognize cellular waste that needs to be degraded, is required to induce liver cancer in mice.

The research team looked at noncancerous liver samples from people who previously underwent treatment to destroy liver cancer. They found that people with high levels of p62 were more likely to see their cancer return and less likely to survive cancer-free than people with low or no p62. They then investigated the protein in mice and discovered that p62 activated other proteins and genes that help stressed cells survive, allowing the cells to live longer and accumulate cancer-causing mutations, ultimately forming tumors. Because liver tumors could not form without the protein, study authors suggested that molecules interfering with p62 may be useful for preventing the progression of chronic liver disease to liver cancer.

The protein p62 is known to be elevated in many different cancers, including in the liver, but its role in cancer has not been clearly understood. This study shows that p62 is necessary to induce liver cancer in mice and is associated with cancer recurrence in humans, suggesting that it could be used to predict the course of the disease and as a potential therapeutic target for liver cancer.

Citation: Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M. 2016. p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells. Cancer Cell. 29(6):935-948.