Skip to main content

Advertisement

SpringerLink
Log in

Reduced MTA1 Expression by RNAi Inhibits in Vitro Invasion and Migration of Esophageal Squamous Cell Carcinoma Cell Line

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

To distinguish aggressive esophageal squamous cell carcinoma from indolent disease is the important clinical challenge. Studies have indicated that metastasis-associated gene 1(Mta1) played a role in the process of metastasis of carcinoma. The overexpression of Mta1 gene has been found in a variety of tumors. To identify the detailed roles of MTA1 protein in the carcinogenesis of esophageal squamous cell carcinoma, this study analyzed the pathological specimens on tissue microarray derived from 72 patients using immunohistochemistry. MTA1 expression increased in the nuclear with the development of esophageal squamous cell carcinoma from normal epithelial cell, dysplasia, to invasive cancer. In biological studies with human esophageal squamous cell carcinoma cell line, MTA1 plays its roles to promote cancer cell invasion, adhesion and movement. RNA interference (RNAi) against MTA1 decreased the malignant phenotypes. Gene microarray analysis revealed some metastasis-associated genes were altered by MTA1 RNAi. This study started an effective beginning to explore metastasis mechanisms and cancer gene therapy strategy targeting MTA1.

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

Similar content being viewed by others

Abbreviations

Mta1:

metastasis-associated gene 1

RNAi:

RNA interference

siRNA:

small interfering RNA

MTA1-siRNA:

small interfering RNA for MTA1

Control-siRNA:

small interfering RNA for control PBS phosphate buffered saline

TSLC1:

tumor suppressor in lung cancer 1

VEGF:

vascular endothelial growth factor

GAPDH:

Glyseraldehyde-3-phosphate dehydrogenase

MDM2:

murine double minute 2

HDAC:

histone deacetylase

MMP:

Matrix Metalloproteinase

RT-PCR:

reverse transcription-polymerase chain reaction

References

  1. Sugimachi K, Matsuoka H, Ohno S et al (1988) Multivariate approach for assessing the prognosis of clinical oesophageal carcinoma. Br J Surg 75:1115–1118

    Article  PubMed  CAS  Google Scholar 

  2. Yoshinaga K, Inoue H, Utsunomiya T et al (2004) N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma. Clin Cancer Res 10:5702–5707

    Article  PubMed  CAS  Google Scholar 

  3. Ito T, Shimada Y, Hashimoto Y et al (2003) Involvement of TSLC1 in progression of esophageal squamous cell carcinoma. Cancer Res 63:6320–6326

    PubMed  CAS  Google Scholar 

  4. Kato H, Yoshikawa M, Miyazaki T et al (2002) Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) in esophageal squamous cell carcinoma. Anticancer Res 22:3977–3984

    PubMed  CAS  Google Scholar 

  5. Song IH (2004) Cancer metastasis and metastasis suppressors. Korean J Gastroenterol 43:1–7

    PubMed  Google Scholar 

  6. Stracke ML, Liotta LA (1992) Multi-step cascade of tumor cell metastasis. In Vivo 6:309–316

    PubMed  CAS  Google Scholar 

  7. Toh Y, Pencil SD, Nicolson GL (1994) A novel candidate metastasis-associated gene, MTA1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem 269:22958–22963

    PubMed  CAS  Google Scholar 

  8. Mazumdar A, Wang RA, Mishra SK et al (2001) Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3:30–37

    Article  PubMed  CAS  Google Scholar 

  9. Yan C, Wang H, Toh Y et al (2003) Repression of 92-kDa type IV collagenase expression by MTA1 is mediated through direct interactions with the promoter via a mechanism, which is both dependent on and independent of histone deacetylation. J Biol Chem 278:2309–2316

    Article  PubMed  CAS  Google Scholar 

  10. Nicolson GL, Nawa A, Toh Y et al (2003) Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis 20:19–24

    Article  PubMed  CAS  Google Scholar 

  11. Toh Y, Kuwano H, Mori M et al (1999) Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer 79:1723–1726

    Article  PubMed  CAS  Google Scholar 

  12. Sasaki H, Yukiue H, Kobayashi Y et al (2001) Expression of the MTA1 mRNA in thymoma patients. Cancer Lett 174:159–163

    Article  PubMed  CAS  Google Scholar 

  13. Sasaki H, Moriyama S, Nakashima Y et al (2002) Expression of the MTA1 mRNA in advanced lung cancer. Lung Cancer 35:149–154

    Article  PubMed  Google Scholar 

  14. Hao XP, Pretlow TG, Rao JS et al (2001) Beta-catenin expression is altered in human colonic aberrant crypt foci. Cancer Res 61:8085–8088

    PubMed  CAS  Google Scholar 

  15. Shimada Y, Imamura M, Wagata T et al (1992) Characterization of 21 newly established esophageal cancer cell lines. Cancer 69:277–284

    Article  PubMed  CAS  Google Scholar 

  16. Huet E, Brassart B, Cauchard JH et al (2002) Cumulative influence of elastin peptides and plasminogen on matrix metalloproteinase activation and type I collagen invasion by HT-1080 fibrosarcoma cells. Clin Exp Metastasis 19:107–117

    Article  PubMed  CAS  Google Scholar 

  17. Inoue T, Geyer RK, Howard D et al (2001) MDM2 can promote the ubiquitination, nuclear export, and degradation of p53 in the absence of direct binding. J Biol Chem 276:45255–45260

    Article  PubMed  CAS  Google Scholar 

  18. Fuchs SY, Adler V, Buschmann T et al (1998) Mdm2 association with p53 targets its ubiquitination. Oncogene 17:2543–2547

    Article  PubMed  CAS  Google Scholar 

  19. Nair KS, Naidoo R, Chetty R (2005) Expression of cell adhesion molecules in oesophageal carcinoma and its prognostic value. J␣Clin Pathol 58:343–351

    Article  PubMed  CAS  Google Scholar 

  20. Kuwano H, Kato H, Miyazaki T et al (2005) Genetic alterations in esophageal cancer. Surg Today 35:7–18

    Article  PubMed  Google Scholar 

  21. Yokozaki H, Tahara E (1994) Metastasis-related genes. Gan To Kagaku Ryoho 21:2541–2548

    PubMed  CAS  Google Scholar 

  22. Hofer MD, Kuefer R, Varambally S et al (2004) The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res 64:825–829

    Article  PubMed  CAS  Google Scholar 

  23. Moon WS, Chang K, Tarnawski AS (2004) Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: Relationship to vascular invasion and estrogen receptor-alpha. Hum Pathol 35:424–429

    Article  PubMed  CAS  Google Scholar 

  24. Yi S, Guangqi H, Guoli H (2003) The association of the expression of MTA1, nm23H1 with the invasion, metastasis of ovarian carcinoma. Chin Med Sci J 18:87–92

    PubMed  Google Scholar 

  25. Mahoney MG, Simpson A, Jost M et al (2002) Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes. Oncogene 21:2161–2170

    Article  PubMed  CAS  Google Scholar 

  26. Hofer MD, Menke A, Genze F et al (2004) Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. Br J Cancer 90:455–462

    Article  PubMed  CAS  Google Scholar 

  27. Mishra SK, Mazumdar A, Vadlamudi RK et al (2003) MICoA, a novel metastasis-associated protein 1 (MTA1) interacting protein coactivator, regulates estrogen receptor-alpha transactivation functions. J Biol Chem 278:19209–19219

    Article  PubMed  CAS  Google Scholar 

  28. Talukder AH, Mishra SK, Mandal M et al (2003) MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates estrogen receptor transactivation functions. J Biol Chem 278:11676–11685

    Article  PubMed  CAS  Google Scholar 

  29. Toh Y, Ohga T, Endo K et al (2004) Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. Int J Cancer 110:362–367

    Article  PubMed  CAS  Google Scholar 

  30. Oda T, Kanai Y, Oyama T et al (1994) E-cadherin gene mutations in human gastric carcinoma cell lines. Proc Natl Acad Sci USA 91:1858–1862

    Article  PubMed  CAS  Google Scholar 

  31. Young JD, Ramsey JC, Braun WH (1981) Pharmacokinetics of 2,4,5-T PGBE ester applied dermally to rats. J Toxicol Environ Health 8:401–408

    Article  PubMed  CAS  Google Scholar 

  32. Somasundar P, Yu AK, Vona-Davis L et al (2003) Differential effects of leptin on cancer in vitro. J Surg Res 113:50–55

    Article  PubMed  CAS  Google Scholar 

  33. Oren M, Damalas A, Gottlieb T et al (2002) Regulation of p53: intricate loops and delicate balances. Biochem Pharmacol 64:865–871

    Article  PubMed  CAS  Google Scholar 

  34. Blagosklonny MV, Trostel S, Kayastha G et al (2005) Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors. Cancer Res 65:7386–7392

    Article  PubMed  CAS  Google Scholar 

  35. Denlinger CE, Keller MD, Mayo MW et al (2004) Combined proteasome and histone deacetylase inhibition in non-small cell lung cancer. J Thorac Cardiovasc Surg 127:1078–1086

    Article  PubMed  CAS  Google Scholar 

  36. Warrell RP Jr, He LZ, Richon V et al (1998) Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Natl Cancer Inst 90:1621–1625

    Article  PubMed  CAS  Google Scholar 

  37. Phillips T, Collins T, Davies J (2005) American Association for Cancer Research – 96th Annual Meeting. Targeting the cell cycle and HDAC inhibitors. IDrugs 8:450–453

    PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. M.G. Mahoney (Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania) for the kind supply of plasmid pcDNA3-MTA1 and Dr. Shimada Y for the KYSE esophageal cancer cells (Kyoto University Graduate School of Medicine, Japan). The thesis was supported by the National Key Basic Research Program (NKBRP) (973 program) (No. 2002CB513100-8). We gratefully appreciate the support.

Author information

Authors and Affiliations

  1. State Key Laboratory of Molecular Oncology, Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan Nanli, Chao Yang District, Beijing, 100021, China

    Haili Qian, Ning Lu, Xiao Liang, Xueyan Zhang, Ming Fu, Qimin Zhan, Zhihua Liu & Chen Lin

  2. Department of pathology, Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17 Panjiayuan Nanli, Chao Yang District, Beijing, 100021, China

    Liyan Xue & Yongqiang Xie

Authors
  1. Haili Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ning Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liyan Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xueyan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongqiang Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qimin Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhihua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chen Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chen Lin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qian, H., Lu, N., Xue, L. et al. Reduced MTA1 Expression by RNAi Inhibits in Vitro Invasion and Migration of Esophageal Squamous Cell Carcinoma Cell Line. Clin Exp Metastasis 22, 653–662 (2005). https://doi.org/10.1007/s10585-006-9005-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-006-9005-2

Keywords

Search

Navigation