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 Jeng & 7 others Jennifer L. Hsu, Long Yuan Li, Alai Tan, Steven A. Curley, Lee M. Ellis, Raymond N. DuBois, Mien Chie Hung

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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

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Colorectal Neoplasms
Neoplasm Metastasis
Liver
Genes
Liver Neoplasms
Cause of Death
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. / Ding, Qingqing; Chang, Chun Ju; Xie, Xiaoming; Xia, Weiya; Yang, Jer Yen; Wang, Shao Chun; Wang, Yan; Xia, Jiahong; Chen, Libo; Cai, Changchung; Li, Huabin; Yen, Chia Jui; Kuo, Hsu Ping; Lee, Dung Fang; Lang, Jingyu; Huo, Longfei; Cheng, Xiaoyun; Chen, Yun Ju; Li, Chia Wei; Jeng, Long Bin; Hsu, Jennifer L.; Li, Long Yuan; Tan, Alai; Curley, Steven A.; Ellis, Lee M.; DuBois, Raymond N.; Hung, Mien Chie.

In: Journal of Clinical Investigation, Vol. 121, No. 11, 01.11.2011, p. 4526-4536.

Research output: Contribution to journalArticle

Ding, Q, Chang, CJ, Xie, X, Xia, W, Yang, JY, Wang, SC, Wang, Y, Xia, J, Chen, L, Cai, C, Li, H, Yen, CJ, Kuo, HP, Lee, DF, Lang, J, Huo, L, Cheng, X, Chen, YJ, Li, CW, Jeng, LB, Hsu, JL, Li, LY, Tan, A, Curley, SA, Ellis, LM, DuBois, RN & Hung, MC 2011, 'APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis', Journal of Clinical Investigation, vol. 121, no. 11, pp. 4526-4536. https://doi.org/10.1172/JCI45008
Ding, Qingqing ; Chang, Chun Ju ; Xie, Xiaoming ; Xia, Weiya ; Yang, Jer Yen ; Wang, Shao Chun ; Wang, Yan ; Xia, Jiahong ; Chen, Libo ; Cai, Changchung ; Li, Huabin ; Yen, Chia Jui ; Kuo, Hsu Ping ; Lee, Dung Fang ; Lang, Jingyu ; Huo, Longfei ; Cheng, Xiaoyun ; Chen, Yun Ju ; Li, Chia Wei ; Jeng, Long Bin ; Hsu, Jennifer L. ; Li, Long Yuan ; Tan, Alai ; Curley, Steven A. ; Ellis, Lee M. ; DuBois, Raymond N. ; Hung, Mien Chie. / APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 11. pp. 4526-4536.
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title = "APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis",
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.",
author = "Qingqing Ding and Chang, {Chun Ju} and Xiaoming Xie and Weiya Xia and Yang, {Jer Yen} and Wang, {Shao Chun} and Yan Wang and Jiahong Xia and Libo Chen and Changchung Cai and Huabin Li and Yen, {Chia Jui} and Kuo, {Hsu Ping} and Lee, {Dung Fang} and Jingyu Lang and Longfei Huo and Xiaoyun Cheng and Chen, {Yun Ju} and Li, {Chia Wei} and Jeng, {Long Bin} and Hsu, {Jennifer L.} and Li, {Long Yuan} and Alai Tan and Curley, {Steven A.} and Ellis, {Lee M.} and DuBois, {Raymond N.} and Hung, {Mien Chie}",
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T1 - APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis

AU - Ding, Qingqing

AU - Chang, Chun Ju

AU - Xie, Xiaoming

AU - Xia, Weiya

AU - Yang, Jer Yen

AU - Wang, Shao Chun

AU - Wang, Yan

AU - Xia, Jiahong

AU - Chen, Libo

AU - Cai, Changchung

AU - Li, Huabin

AU - Yen, Chia Jui

AU - Kuo, Hsu Ping

AU - Lee, Dung Fang

AU - Lang, Jingyu

AU - Huo, Longfei

AU - Cheng, Xiaoyun

AU - Chen, Yun Ju

AU - Li, Chia Wei

AU - Jeng, Long Bin

AU - Hsu, Jennifer L.

AU - Li, Long Yuan

AU - Tan, Alai

AU - Curley, Steven A.

AU - Ellis, Lee M.

AU - DuBois, Raymond N.

AU - Hung, Mien Chie

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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.

AB - 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.

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