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Activating transcription factor 3 promotes colon cancer metastasis

  • Research Article
  • Published:
Tumor Biology

Abstract

Colorectal cancer is one of the commonest of solid malignancy in the world. Activating transcription factor 3 (ATF3), a homolog of the mouse TI-241 and rat LFR-1, is a stress responsive gene that has been widely indicated in different malignancies. However, the role of ATF3 in colon cancer is paradoxical with both a suggested pro- and anti-tumorigenic role. The objective of the current study was to investigate the role of ATF3 in colon cancer metastasis using HT29 and CaCO2 colon cancer cell lines. Expression of ATF3 was initially evaluated in five pairs of colon cancer and matched noncancerous colon tissues. The role of ATF3 in promoting in vitro migration and invasion were evaluated by siRNA-mediated knockdown and adenovirus-mediated overexpression of ATF3. In addition, the role of ATF3 in promoting in vivo tumor growth and hepatic metastasis was investigated by shRNA-mediated knockdown of ATF3. Expression of ATF3 was more in the colon cancer tissues as compared with the pooled noncancerous control colon tissue. Our results showed that in both HT29 and CaCO2 cells, ATF3 promoted in vitro motility and invasion. Furthermore, knockdown of ATF3 attenuated subcutaneous tumor growth and CD31+ neovasculature in xenograft assays with HT29 and CaCO2 cells and inhibited hepatic metastasis. Cumulatively, our results unequivocally show that ATF3 promotes colon cancer metastasis.

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Abbreviations

ATF3:

Activating transcription factor 3

MOI:

Multiplicity of infection

SEM:

Standard error of mean

MSI:

Microsatellite instability

CIMP:

CpG island methylator phenotype

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Authors and Affiliations

  1. Department of Oncology, Chinese PLA General Hospital, Beijing, China

    Zhi-Yong Wu, Sheng-Jie Sun, Jing Yuan & Shun-Chang Jiao

  2. Department of Radiology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing, China

    Zheng-mao Wei

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  1. Zhi-Yong Wu
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  2. Zheng-mao Wei
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  3. Sheng-Jie Sun
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  4. Jing Yuan
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  5. Shun-Chang Jiao
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Correspondence to Shun-Chang Jiao.

Additional information

Zhi-Yong Wu and Zheng-mao Wei contributed equally to this work.

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Wu, ZY., Wei, Zm., Sun, SJ. et al. Activating transcription factor 3 promotes colon cancer metastasis. Tumor Biol. 35, 8329–8334 (2014). https://doi.org/10.1007/s13277-014-2044-4

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  • DOI: https://doi.org/10.1007/s13277-014-2044-4

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