Document Type
Article
Date of Original Version
2019
Abstract
Tumors display profound changes in cellular metabolism, yet how these changes aid the development and growth of tumors is not fully understood. Here we use a multi-omic approach to examine liver carcinogenesis and regeneration, and find that progressive loss of branched-chain amino acid (BCAA) catabolism promotes tumor development and growth. In human hepatocellular carcinomas and animal models of liver cancer, suppression of BCAA catabolic enzyme expression led to BCAA accumulation in tumors, though this was not observed in regenerating liver tissues. The degree of enzyme suppression strongly correlated with tumor aggressiveness, and was an independent predictor of clinical outcome. Moreover, modulating BCAA accumulation regulated cancer cell proliferation in vitro, and tumor burden and overall survival in vivo. Dietary BCAA intake in humans also correlated with cancer mortality risk. In summary, loss of BCAA catabolism in tumors confers functional advantages, which could be exploited by therapeutic interventions in certain cancers.
Citation/Publisher Attribution
Erickson, R. E., Lim, S. L., McDonnell, E., Shuen, W. H., Vadiveloo, M., White, P. J., Ding, Z.,...Han, W. (2019). Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression. Cell Metabolism, 29(5), 1151-1165. doi: 10.1016/j.cmet.2018.12.020
Available at: https://doi.org/10.1016/j.cmet.2018.12.020
Author Manuscript
This is a pre-publication author manuscript of the final, published article.
Terms of Use
This article is made available under the terms and conditions applicable
towards Open Access Policy Articles, as set forth in our Terms of Use.