Skip to main content
Log in

RETRACTED ARTICLE: Downregulation of nicotinamide N-methyltransferase inhibits migration and epithelial-mesenchymal transition of esophageal squamous cell carcinoma via Wnt/β-catenin pathway

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

This article was retracted on 08 February 2024

A Correction to this article was published on 18 July 2020

This article has been updated

Abstract

Nicotinamide N-methyltransferase (NNMT) is an important methyltransferase involved in the biotransformation of many drugs and exogenous compounds. Abnormal expression of NNMT protein is closely associated with the onset and progression of many malignancies, but little is known about its role in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to explore whether NNMT plays any roles in carcinogenesis and metastasis in ESCC. NNMT expression was determined by immunohistochemistry in ESCC and corresponding adjacent normal tissues. Functional experiments were performed to elucidate the effects of NNMT knockdown on the proliferation, apoptosis, cell cycle, migration, and epithelial-mesenchymal transition (EMT) in EC9706 and TE1 cells. NNMT expression was significantly elevated in ESCC tissues compared with corresponding adjacent normal tissues. Moreover, a significant association emerged between NNMT expression and lymph node metastasis. SiRNA-mediated knockdown of NNMT in ESCC cells can significantly suppress cell viability and migration, induce cell cycle arrest, and promote cell apoptosis. In addition, NNMT downregulation led to the reversal of EMT, as reflected by upregulation of the intercellular adhesion molecule E-cadherin and downregulation of the mesenchymal markers N-cadherin and Vimentin. Further study found that NNMT knockdown suppressed the Wnt/β-catenin signaling pathway. Taken together, these findings indicate that NNMT is a critical regulator of EMT in ESCC and may be a potential therapeutic target for ESCC metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Change history

References

  1. Chen W, Zheng R, Zuo T et al (2012) National cancer incidence and mortality in China. Chin J Cancer Res 28(1):1–11

    Google Scholar 

  2. Pennathur A, Gibson MK, Jobe BA et al (2013) Oesophageal carcinoma. LANCET 381(9864):400–412

    Article  PubMed  Google Scholar 

  3. Zeng H, Zheng R, Zhang S et al (2016) Esophageal cancer statistics in China, 2011: estimates based on 177 cancer registries. Thorac Cancer 7(2):232–237

    Article  PubMed  Google Scholar 

  4. Wang H, Deng F, Liu Q et al (2017) Prognostic significance of lymph node metastasis in esophageal squamous cell carcinoma. Pathol Res Pract 213(7):842–847

    Article  PubMed  Google Scholar 

  5. Haslehurst AM, Koti M, Dharsee M et al (2012) EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer 12:91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Feng H, Liu Q, Zhang N et al (2013) Leptin promotes metastasis by inducing an epithelial-mesenchymal transition in A549 lung cancer cells. Oncol Res 21(3):165–171

    Article  PubMed  Google Scholar 

  7. Chen C, Wang X, Huang X et al (2016) Nicotinamide N-methyltransferase: a potential biomarker for worse prognosis in gastric carcinoma. Am J Cancer Res 6(3):649–663

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Aksoy S, Szumlanski CL, Weinshilboum RM (1994) Human liver nicotinamide N-methyltransferase. cDNA cloning, expression, and biochemical characterization. J Biol Chem 269(20):14835–14840

    Article  CAS  PubMed  Google Scholar 

  9. Xu JM, Moatamed F, Caldwell JS et al (2003) Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells. J Clin Endocrinol Metab 88(10):4990–4996

    Article  CAS  PubMed  Google Scholar 

  10. Yao M, Tabuchi H, Nagashima Y et al (2005) Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. J Pathol 205(3):377–387

    Article  CAS  PubMed  Google Scholar 

  11. Kim J, Hong SJ, Lim EK et al (2009) Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis. J Exp Clin Cancer Res 28:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Roessler M, Rollinger W, Palme S et al (2005) Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer. Clin Cancer Res 11(18):6550–6557

    Article  CAS  PubMed  Google Scholar 

  13. Emanuelli M, Santarelli A, Sartini D et al (2010) Nicotinamide N-methyltransferase upregulation correlates with tumour differentiation in oral squamous cell carcinoma. Histol Histopathol 25(1):15–20

    CAS  PubMed  Google Scholar 

  14. Sartini D, Morganti S, Guidi E et al (2013) Nicotinamide N-methyltransferase in non-small cell lung cancer: promising results for targeted anti-cancer therapy. Cell Biochem Biophys 67(3):865–873

    Article  CAS  PubMed  Google Scholar 

  15. Loos M, Hedderich DM, Ottenhausen M et al (2009) Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer. BMC Cancer 9:463

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yu T, Wang Y-T, Chen P et al (2015) Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress. Cell Physiol Biochem 35(2):710–721

    Article  CAS  PubMed  Google Scholar 

  17. Tang S-W, Yang T-C, Lin W-C et al (2011) Nicotinamide N-methyltransferase induces cellular invasion through activating matrix metalloproteinase-2 expression in clear cell renal cell carcinoma cells. Carcinogenesis 32(2):138–145

    Article  CAS  PubMed  Google Scholar 

  18. Wu Y, Siadaty MS, Berens ME et al (2008) Overlapping gene expression profiles of cell migration and tumor invasion in human bladder cancer identify metallothionein 1E and nicotinamide N-methyltransferase as novel regulators of cell migration. Oncogene 27(52):6679–6689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pozzi V, Mazzotta M, Lo Muzio L et al (2011) Inhibiting proliferation in KB cancer cells by RNA interference-mediated knockdown of nicotinamide N-methyltransferase expression. Int J Immunopathol Pharmacol 24(1):69–77

    Article  CAS  PubMed  Google Scholar 

  20. Zhang J, Wang Y, Li G et al (2014) Down-regulation of nicotinamide N-methyltransferase induces apoptosis in human breast cancer cells via the mitochondria-mediated pathway. PLoS ONE 9(2):e89202

    Article  PubMed  PubMed Central  ADS  Google Scholar 

  21. Davis FM, Stewart TA, Thompson EW et al (2014) Targeting EMT in cancer: opportunities for pharmacological intervention. Trends Pharmacol Sci 35(9):479–488

    Article  CAS  PubMed  Google Scholar 

  22. Liang L, Zeng M, Pan H et al (2018) Nicotinamide N-methyltransferase promotes epithelial-mesenchymal transition in gastric cancer cells by activating transforming growth factor-beta 1 expression. Oncol Lett 15(4):4592–4598

    PubMed  PubMed Central  Google Scholar 

  23. Douchi D, Ohtsuka H, Ariake K et al (2015) Silencing of LRRFIP1 reverses the epithelial-mesenchymal transition via inhibition of the Wnt/beta-catenin signaling pathway. Cancer Lett 365(1):132–140

    Article  CAS  PubMed  Google Scholar 

  24. Zhang J, Wen X, Ren X-Y et al (2016) YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/beta-catenin signaling pathway. J Exp Clin Cancer Res 35:109

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lu Y-J, Geng Z-J, Sun X-Y et al (2015) Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells. Mol Cell Biochem 408(1–2):1–13

    Article  CAS  PubMed  Google Scholar 

  26. Scaglia N, Igal RA (2008) Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis. Int J Oncol 33(4):839–850

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Henan Natural Science Foundation (Grant No. 182300410377), the Key Scientific Research Projects of Henan Higher Education institutions (Grant No. 17A180016), and the National Natural Science Foundation of China (Grant No. 81272691).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yanting Zhang or Fangxia Guan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s11010-024-04959-5"

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cui, Y., Zhang, L., Wang, W. et al. RETRACTED ARTICLE: Downregulation of nicotinamide N-methyltransferase inhibits migration and epithelial-mesenchymal transition of esophageal squamous cell carcinoma via Wnt/β-catenin pathway. Mol Cell Biochem 460, 93–103 (2019). https://doi.org/10.1007/s11010-019-03573-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-019-03573-0

Keywords

Navigation