Tumor Biology

, Volume 34, Issue 6, pp 3649–3657 | Cite as

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

  • Yuchan Wang
  • Shuhui Zhou
  • Xiaojing Yang
  • Hui Shi
  • Mei Li
  • Qun Xue
  • Xianting Huang
  • Xinxiu Wang
  • Huijie Wang
  • Jianguo Zhang
Research Article
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Accepted:

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.

Keywords

Esophageal squamous cell carcinoma (ESCC) CREM-1 Migration 
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Notes

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).

Conflicts of interest

None

References

  1. 1.
    Hu WM, Li L, Jing BQ, et al. Effect of S1P5 on proliferation and migration of human esophageal cancer cells. World J Gastroenterol. 2010;16:1859–66.PubMedCrossRefGoogle Scholar
  2. 2.
    Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Wang X, Tian X, Liu F, et al. Detection of HPV DNA in esophageal cancer specimens from different regions and ethnic groups: a descriptive study. BMC Cancer. 2010;10:19.PubMedCrossRefGoogle Scholar
  4. 4.
    Gu Y, Lin S, Li JL, et al. Altered LKB1/CREB-regulated transcription co-activator (CRTC) signaling axis promotes esophageal cancer cell migration and invasion. Oncogene. 2012;31:469–79.PubMedCrossRefGoogle Scholar
  5. 5.
    Katoh Y, Takemori H, Lin XZ, et al. Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade. FEBS J. 2006;273:2730–48.PubMedCrossRefGoogle Scholar
  6. 6.
    Persengiev SP, Green MR. The role of ATF/CREB family members in cell growth, survival and apoptosis. Apoptosis. 2003;8:225–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Herdegen T, Leah JD. Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev. 1998;28:370–490.PubMedCrossRefGoogle Scholar
  8. 8.
    Wilson BE, Mochon E, Boxer LM. Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol Cell Biol. 1996;16:5546–56.PubMedGoogle Scholar
  9. 9.
    Wu X, Jin W, Liu X, et al. Cyclic AMP response element modulator-1 (CREM-1) involves in neuronal apoptosis after traumatic brain injury. J Mol Neurosci. 2012;47:357–67.PubMedCrossRefGoogle Scholar
  10. 10.
    Union Internationale Contre le Cancer (UICC), the American Joint Committee on Cancer (AJCC). Workshop on Diagnosis and Prognosis of Renal Cell Carcinoma. Rochester, Minnesota. Cancer. 1997;80:973–1000.Google Scholar
  11. 11.
    Yu C, Chen K, Zheng H, et al. Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis. Carcinogenesis. 2009;30:894–901.PubMedCrossRefGoogle Scholar
  12. 12.
    Shi GZ, Yuan Y, Jiang GJ, et al. PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma. BMC Cancer. 2012;12:97.PubMedCrossRefGoogle Scholar
  13. 13.
    Lin CS, Lee HT, Lee SY, et al. High mitochondrial DNA copy number and bioenergetic function are associated with tumor invasion of esophageal squamous cell carcinoma cell lines. Int J Mol Sci. 2012;13:11228–46.PubMedCrossRefGoogle Scholar
  14. 14.
    Eccles SA, Welch DR. Metastasis: recent discoveries and novel treatment strategies. Lancet. 2007;369:1742–57.PubMedCrossRefGoogle Scholar
  15. 15.
    Chuangui C, Peng T, Zhentao Y. The expression of high mobility group box 1 is associated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma. Pathol Oncol Res. 2012;18:1021–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.PubMedCrossRefGoogle Scholar
  18. 18.
    Allagnat F, Martin D, Condorelli DF, Waeber G, Haefliger JA. Glucose represses connexin36 in insulin-secreting cells. J Cell Sci. 2005;118:5335–44.PubMedCrossRefGoogle Scholar
  19. 19.
    Guo Z, Du X, Iacovitti L. Regulation of tyrosine hydroxylase gene expression during transdifferentiation of striatal neurons: changes in transcription factors binding the AP-1 site. J Neurosci. 1998;18:8163–74.PubMedGoogle Scholar
  20. 20.
    He Z, Jiang J, Kokkinaki M, Golestaneh N, Hofmann MC, Dym M. Gdnf upregulates c-Fos transcription via the Ras/Erk1/2 pathway to promote mouse spermatogonial stem cell proliferation. Stem Cells. 2008;26:266–78.PubMedCrossRefGoogle Scholar
  21. 21.
    Sawka-Verhelle D, Escoubet-Lozach L, Fong AL, et al. PE-1/METS, an antiproliferative Ets repressor factor, is induced by CREB-1/CREM-1 during macrophage differentiation. J Biol Chem. 2004;279:17772–84.PubMedCrossRefGoogle Scholar
  22. 22.
    Salnikov AV, Liu L, Platen M, et al. Hypoxia induces EMT in low and highly aggressive pancreatic tumor cells but only cells with cancer stem cell characteristics acquire pronounced migratory potential. PLoS One. 2012;7:e46391.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Yuchan Wang
    • 1
  • Shuhui Zhou
    • 2
  • Xiaojing Yang
    • 1
  • Hui Shi
    • 3
  • Mei Li
    • 3
  • Qun Xue
    • 3
  • Xianting Huang
    • 1
  • Xinxiu Wang
    • 1
  • Huijie Wang
    • 4
  • Jianguo Zhang
    • 3
  1. 1.Department of Pathogen Biology, Medical CollegeNantong UniversityNantongPeople’s Republic of China
  2. 2.Department of Radiation Medicine and Protection, Medical CollegeSoohow UniversitySuzhouPeople’s Republic of China
  3. 3.Department of PathologyAffiliated Hospital of Nantong UniversityNantongChina
  4. 4.Department of Medical OncologyFudan University Shanghai Cancer CenterShanghaiPeople’s Republic of China

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