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Low expression of cyclic amp response element modulator-1 can increase the migration and invasion of esophageal squamous cell carcinoma

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Tumor Biology

Abstract

Cyclic AMP response element-binding protein (CREB) family can regulate biological functions of various types of cells and has relation with esophageal cancer cell migration and invasion. Cyclic AMP response element modulator-1 (CREM-1) is one member of the family with limited acquaintance. This study was conducted to investigate the effect of CREM-1 on migration and invasion in human esophageal squamous cell carcinoma (ESCC). The expression of CREM-1 protein in ESCC tissues with or without lymph nodes metastasis was determined by western blot. Immunohistochemical analysis of CREM-1 expression were carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The roles of CREM-1 in migration and invasion were studied in TE1 cells through knocking CREM-1 down with siRNA or overexpression of CREM-1 in ECA109 cells. The regulations of CREM-1 on invasion and migration were determined by transwell and wounding healing assay. The effect of CREM-1 on chemotherapy drug was analyzed by Cell counting kit-8 assay. We found that the expression of CREM-1 was significantly downregulated in ESCC tissues with lymph nodes metastasis compared with the tissues without lymph nodes metastasis and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, knocking CREM-1 down with siRNA increased cell migration and invasion in human ESCC cell lines TE1 while upregulation of CREM-1 inhibited the motility. Our data suggested that CREM-1 might play an important role in the regulation of tumor metastasis and invasion and serve as a tumor suppressor in human ESCC. We proposed that CREM-1 might be used as a potential therapeutic agent for human ESCC.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81201858) and Natural Scientific Foundation of Jiangsu Province Grant (No. BK2012231); a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China

    Yuchan Wang, Xiaojing Yang, Xianting Huang & Xinxiu Wang

  2. Department of Radiation Medicine and Protection, Medical College, Soohow University, Suzhou, Jiangsu, 215123, People’s Republic of China

    Shuhui Zhou

  3. Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Hui Shi, Mei Li, Qun Xue & Jianguo Zhang

  4. Department of Medical Oncology, Fudan University Shanghai Cancer Center, No 270 Dongan Road, Shanghai, 200032, People’s Republic of China

    Huijie Wang

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  1. Yuchan Wang
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  2. Shuhui Zhou
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  3. Xiaojing Yang
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  4. Hui Shi
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  5. Mei Li
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  7. Xianting Huang
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  8. Xinxiu Wang
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  9. Huijie Wang
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  10. Jianguo Zhang
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Corresponding authors

Correspondence to Huijie Wang or Jianguo Zhang.

Additional information

Yuchan Wang and Shuhui Zhou contributed equally to this work.

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Wang, Y., Zhou, S., Yang, X. et al. Low expression of cyclic amp response element modulator-1 can increase the migration and invasion of esophageal squamous cell carcinoma. Tumor Biol. 34, 3649–3657 (2013). https://doi.org/10.1007/s13277-013-0946-1

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  • DOI: https://doi.org/10.1007/s13277-013-0946-1

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