Skip to main content
SpringerLink
Log in

Overexpression of S-adenosylhomocysteine hydrolase (SAHH) in esophageal squamous cell carcinoma (ESCC) cell lines: effects on apoptosis, migration and adhesion of cells

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

S-adenosylhomocysteine hydrolase (SAHH) is the sole enzyme that catalyses the hydrolysis of S-adenosylhomocysteine (SAH) in methylation reaction. Previous studies have shown that its inhibition or deficiency leads to several human disorders such as severe coagulopathy, hepatopathy and myopathy. However, the effects of SAHH on esophageal squamous cell carcinoma (ESCC) cells have not been explored so far. To determine whether SAHH is involved in carcinogenesis of the esophagus, we investigated the expression of SAHH in ESCC and normal esophageal epithelial cells and found that SAHH was downregulated in ESCC cells compared with normal esophageal epithelial cells (P < 0.05). The overexpressed SAHH in ESCC cells promoted cell apoptosis, inhibited cell migration and adhesion, but did not affect the cell proliferation and cell cycle. Furthermore, an interaction of SAHH with receptor of activated C kinase 1 (RACK1) protein was detected by coimmunoprecipitation and an increased RACK1, which is caused by overexpression of SAHH, was verified by Western blotting. The findings mentioned above demonstrate that SAHH can promote apoptosis, inhibit migration and adhesion of ESCC cells suggesting that it may be involved in carcinogenesis of the esophagus.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Hou GQ, Zhang Q, Wang LL, Liu MY, Wang JR, Xue LX (2010) mTOR inhibitor rapamycin alone or combined with cisplatin inhibits growth of esophageal squamous cell carcinoma in nude mice. Cancer Lett 290:248–254

    Article  PubMed  CAS  Google Scholar 

  2. Nakanishi M (2007) S-adenosyl-l-homocysteine hydrolase as an attractive target for antimicrobial drugs. J Pharm Soc Jpn 127:977–982

    CAS  Google Scholar 

  3. Tanaka N, Nakanishi M, Kusakabe Y, Shiraiwa K, Yabe S, Ito Y, Kitade Y, Nakamura KT (2004) Crystal structure of S-adenosyl-l-homocysteine hydrolase from the human malaria parasite Plasmodium falciparum. J Mol Biol 343:1007–1017

    Article  PubMed  CAS  Google Scholar 

  4. Zaina S, Lindholm MW, Lund G (2005) Nutrition and aberrant DNA methylation patterns in atherosclerosis: more than just hyperhomocysteinemia? J Nutr 135:5–8

    PubMed  CAS  Google Scholar 

  5. Honzík T, Magner M, Krijt J, Sokolová J, Vugrek O, Belužić R, Barić I, Hansíkova H, Elledera M, Veselá K, Bauerová L, Ondrušková N, Ješina P, Zeman J, Kožich V (2012) Clinical picture of S-adenosylhomocysteine hydrolase deficiency resembles phosphomannomutase 2 deficiency. Mol Genet Metab 107:611–613

    Article  PubMed  CAS  Google Scholar 

  6. Leal JF, Ferrer I, Blanco-Aparicio C, Hernández-Losa J, Ramóny Cajal S, Carnero A, LLeonart ME (2008) S-adenosylhomocysteine hydrolase downregulation contributes to tumorigenesis. Carcinogenesis 29:2089–2095

    Article  PubMed  CAS  Google Scholar 

  7. Hermes M, Osswald H, Riehle R, Piesch C, Kloor D (2008) S-adenosylhomocysteine hydrolase overexpression in HEK-293 cells: effect on intracellular adenosine levels, cell viability, and DNA methylation. Cell Physiol Biochem 22:223–236

    Article  PubMed  CAS  Google Scholar 

  8. Sedding DG, Trőbs M, Reich F, Walke G, Fink L, Haberbosch W, Rau W, Tillmanns H, Preissner KT, Bohle RM, Langheinrich AC (2009) 3-Deazaadenosine prevents smooth muscle cell proliferation and neointimaformation by interfering with Ras signaling. Circ Res 104:1192–1200

    Article  PubMed  CAS  Google Scholar 

  9. Hayden A, Johnson PW, Packham G, Crabb SJ (2011) S-adenosylhomocysteine hydrolase inhibition by 3-deazaneplanocin A analogues induces anti-cancer effects in breast cancer cell lines and synergy with both histonedeacetylase and HER2 inhibition. Breast Cancer Res Treat 127:109–119

    Article  PubMed  CAS  Google Scholar 

  10. Wang LL, Hou GQ, Xue LX, Li J, Wei P, Xu P (2010) Autocrine motility factor receptor signaling pathway promotes cell invasion via activation of ROCK-2 in esophageal squamous cell cancer cells. Cancer Invest 28:993–1003

    Article  PubMed  CAS  Google Scholar 

  11. Li QH, Zhu LQ, Yan YM, Chai DD, Li J, Xue LX (2013) S-Adenosyl homocysteine hydrolase (SAHH) accelerates flagellar regeneration in Dunaliella salina. Curr Microbiol 164:1028–1034

    Google Scholar 

  12. Palmer JL, Abeles RH (1979) The mechanism of action of S-adenosylhomocysteinase. J Biol Chem 254:1217–1226

    PubMed  CAS  Google Scholar 

  13. LLeonart ME, Vidal F, Gallardo D, Diaz-Fuertes M, Rojo F, Cuatrecasas M, López-Vicente L, Kondoh H, Blanco C, Carnero A, RamónyCajal S (2006) New p53 related genes in human tumors: significant down regulation in colon and lung carcinomas. Oncol Rep 16:603–608

    PubMed  CAS  Google Scholar 

  14. Harrington EO, Smeglin A, Parks N, Newton J, Rounds S (2000) Adenosine induces endothelial apoptosis by activating protein tyrosine phosphatase: a possible role of p38 alpha. Am J Physiol 279:733–742

    Google Scholar 

  15. Barry CP, Lind SE (2000) Adenosine-mediated killing of cultured epithelial cancer cells. Cancer Res 60:1887–1894

    PubMed  CAS  Google Scholar 

  16. Hermes M, Osswald H, Kloor D (2007) Role of S-adenosylhomocysteine hydrolase in adenosine-induced apoptosis in HepG2 cells. Exp Cell Res 313:264–283

    Article  PubMed  CAS  Google Scholar 

  17. Borley AC, Hiscox S, Gee J, Smith C, Shaw V, Lee B, Nicholson P (2008) Anti-oestrogens RI. But not oestrogen deprivation promote cellular invasion in intracellular adhesion-deficient breast cancer cells. Breast Cancer Res 10:R103

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Coskun U, Sancak B, Sen I, Bukan N, Tufan MA, Gülbahar O, Sozen S (2006) Serum P-selectin, soluble vascular cell adhesion molecule-I (s-VCAM-I) and soluble intracellular adhesion molecule-I (s-ICAM-I) levels in bladder carcinoma patients with different stages. Int Immunopharmacol 6:672–677

    Article  PubMed  CAS  Google Scholar 

  19. Shi S, Deng YZ, Zhao JS, Ji XD, Shi J, Feng YX, Li G, Li JJ, Zhu D, Koeffler HP, Zhao Y, Xie D (2011) RACK1 promotes non-small-cell lung cancer tumorigenicity through activating sonic hedgehog signaling pathway. J Biochem 287:7845–7858

    Google Scholar 

  20. Wang F, Osawa T, Tsuchida R, Yuasa Y, Shibuya M (2011) Downregulation of receptor for activated C-kinase 1 (RACK1) suppresses tumor growth by inhibiting tumor cell proliferation and tumor-associated angiogenesis. Cancer Sci 102:2007–2013

    Article  PubMed  CAS  Google Scholar 

  21. Deng YZ, Yao F, Li JJ, Mao ZF, Hu PT, Long LY, Li G, Ji XD, Shi S, Guan DX, Feng YY, Cui L, Li DS, Liu Y, Du X, Guo MZ, Xu LY, Li EM, Wang HY, Xie D (2011) RACK1 suppresses gastric tumorigenesis by stabilizing the β-catenin destruction complex. Gastroenterology 142:812–823

    Article  CAS  Google Scholar 

  22. Wang ZY, Chen ZL, Feng M, Shi SS, He J, Dai GH (2011) The relationship between RACK1 expression and clinicopathologic information of esophageal squamous cell carcinoma. J Chin Med 91:1397–1400

    CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the grants from International Science and Technology Cooperation Program of the Ministry of Science and Technology of P.R. China (No. 2007DFA01240), and the National Natural Science Foundation of China (No. 30700014)

Conflict of interest

There are not any conflicts of interest regarding this paper.

Author information

Authors and Affiliations

  1. Laboratory for Cell Biology, The First Affiliated Hospital, Zhengzhou University, 40 Daxue Road, Henan, 450052, China

    Qinghua Li & Lexun Xue

  2. Department of Biology, Zhengzhou University, Henan, 450001, China

    Lihong Mao, Ruili Wang & Lexun Xue

  3. Clinic Laboratory, The Second Affiliated Hospital, Zhengzhou University, Henan, 450052, China

    Liqiang Zhu

Authors
  1. Qinghua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lihong Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruili Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liqiang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lexun Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lexun Xue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Q., Mao, L., Wang, R. et al. Overexpression of S-adenosylhomocysteine hydrolase (SAHH) in esophageal squamous cell carcinoma (ESCC) cell lines: effects on apoptosis, migration and adhesion of cells. Mol Biol Rep 41, 2409–2417 (2014). https://doi.org/10.1007/s11033-014-3095-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3095-8

Keywords

Search

Navigation