APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis

Qingqing Ding, Chun Ju Chang, Xiaoming Xie, Weiya Xia, Jer Yen Yang, Shao Chun Wang, Yan Wang, Jiahong Xia, Libo Chen, Changchung Cai, Huabin Li, Chia Jui Yen, Hsu Ping Kuo, Dung Fang Lee, Jingyu Lang, Longfei Huo, Xiaoyun Cheng, Yun Ju Chen, Chia Wei Li, Long Bin JengJennifer L. Hsu, Long Yuan Li, Alai Tan, Steven A. Curley, Lee M. Ellis, Raymond N. DuBois, Mien Chie Hung

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Colorectal cancer is the second leading cause of death from cancer in the United States. Metastases in the liver, the most common metastatic site for colorectal cancer, are found in one-third of the patients who die of colorectal cancer. Currently, the genes and molecular mechanisms that are functionally critical in modulating colorectal cancer hepatic metastasis remain unclear. Here, we report our studies using functional selection in an orthotopic mouse model of colorectal cancer to identify a set of genes that play an important role in mediating colorectal cancer liver metastasis. These genes included APOBEC3G, CD133, LIPC, and S100P. Clinically, we found these genes to be highly expressed in a cohort of human hepatic metastasis and their primary colorectal tumors, suggesting that it might be possible to use these genes to predict the likelihood of hepatic metastasis. We have further revealed what we believe to be a novel mechanism in which APOBEC3G promotes colorectal cancer hepatic metastasis through inhibition of miR-29-mediated suppression of MMP2. Together, our data elucidate key factors and mechanisms involved in colorectal cancer liver metastasis, which could be potential targets for diagnosis and treatment.

Original languageEnglish (US)
Pages (from-to)4526-4536
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Ding, Q., Chang, C. J., Xie, X., Xia, W., Yang, J. Y., Wang, S. C., Wang, Y., Xia, J., Chen, L., Cai, C., Li, H., Yen, C. J., Kuo, H. P., Lee, D. F., Lang, J., Huo, L., Cheng, X., Chen, Y. J., Li, C. W., ... Hung, M. C. (2011). APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. Journal of Clinical Investigation, 121(11), 4526-4536. https://doi.org/10.1172/JCI45008