Tumor Biology

, Volume 36, Issue 11, pp 9005–9013 | Cite as

ARMc8 indicates aggressive colon cancers and promotes invasiveness and migration of colon cancer cells

  • Guiyang Jiang
  • Yong Zhang
  • Xiupeng Zhang
  • Chuifeng Fan
  • Liang Wang
  • Hongtao Xu
  • Juanhan Yu
  • Enhua Wang
Research Article

Abstract

Recent studies have implicated ARMc8 in promoting tumor formation in non-small cell lung cancer and breast cancer; however, so far, no studies have revealed the expression pattern or cellular function of ARMc8 in colon cancer. In this study, we used immunohistochemical staining to measure ARMc8 expression in 206 cases of colon cancer and matched adjacent normal colon tissue. Clinically important behaviors of cells, including invasiveness and migration, were evaluated after upregulation of ARMc8 expression in HT29 cells through gene transfection or downregulation of expression in LoVo cells using RNAi. We found that ARMc8 was primarily located in the membrane and cytoplasm of tumor cells, and its expression level was significantly higher in colon cancer in comparison to that in the adjacent normal colon tissues (p < 0.001). ARMc8 expression was closely related to TNM stage (p = 0.006), lymph node metastasis (p = 0.001), and poor prognosis (p = 0.002) of colon cancer. The invasiveness and migration capacity of HT29 cells transfected with ARMc8 were significantly greater than those of control cells (p < 0.001), while ARMc8 siRNA treatment significantly reduced cell invasion and migration in LoVo cells (p < 0.001). Furthermore, we demonstrated that ARMc8 could upregulate the expression of MMP7 and snail and downregulate the expression of p120ctn and α-catenin. Therefore, ARMc8 probably enhanced invasiveness and metastatic capacity by affecting these tumor-associated factors, thereby playing a role in enhancing the tumorigenicity of colon cancer cells. ARMc8 is likely to become a potential therapeutic target for colon cancer.

Keywords

ARMc8 Colon cancer Invasion Migration 

Notes

Acknowledgments

The authors thank Prof. Ishigatsubo Y, Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, for kindly providing ARMc8 pcDNA. This study was supported by the National Natural Science Foundation of China (No. 81402369 to Guiyang Jiang, No. 81272606 to EnhuaWang, No. 81472599 to Chuifeng Fan, No. 81302192 to Liang Wang) and the Natural Science Foundation of Liaoning Province (No. 2013021049 to Yong Zhang).

Conflicts of interest

None

Supplementary material

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References

  1. 1.
    Riggleman B, Wieschaus E, Schedl P. Molecular analysis of the armadillo locus: uniformly distributed transcripts and a protein with novel internal repeats are associated with a Drosophila segment polarity gene. Genes Dev. 1989;3:96–113.CrossRefPubMedGoogle Scholar
  2. 2.
    Coates JC. Armadillo repeat proteins: beyond the animal kingdom. Trends Cell Biol. 2003;13:463–71.CrossRefPubMedGoogle Scholar
  3. 3.
    Hatzfeld M. The armadillo family of structural proteins. Int Rev Cytol. 1999;186:179–224.CrossRefPubMedGoogle Scholar
  4. 4.
    Kobayashi N, Yang J, Ueda A, et al. RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8α and ARMC8β are components of the CTLH complex. Gene. 2007;396:236–47.CrossRefPubMedGoogle Scholar
  5. 5.
    Tomaru K, Ueda A, Suzuki T, et al. Armadillo repeat containing 8alpha binds to HRS and promotes HRS interaction with ubiquitinated proteins. Open Biochem J. 2010;4:1–8.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Suzuki T, Ueda A, Kobayashi N, et al. Proteasome-dependent degradation of alpha-catenin is regulated by interaction with ARMc8alpha. Biochem J. 2008;411(3):581–91.CrossRefPubMedGoogle Scholar
  7. 7.
    Xie C, Jiang G, Fan C, et al. ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway. Tumour Biol. 2014;35(9):8903–11.CrossRefPubMedGoogle Scholar
  8. 8.
    Fan C, Zhao Y, Mao X, et al. Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma. Tumour Biol. 2014;35(11):11337–43.CrossRefPubMedGoogle Scholar
  9. 9.
    Gorlich D, Prehn S, Laskey RA, et al. Isolation of a protein that is essential for the first step of nuclear protein import. Cell. 1994;79:767–78.CrossRefPubMedGoogle Scholar
  10. 10.
    McCrea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991;254:1359–61.CrossRefPubMedGoogle Scholar
  11. 11.
    Franke WW, Goldschmidt MD, Zimbelmann R, et al. Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. Proc Natl Acad Sci U S A. 1989;86:4027–31.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kinzler KW, Nilbert MC, Vogelstein B, et al. Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science. 1991;251:1366–70.CrossRefPubMedGoogle Scholar
  13. 13.
    Groden J, Thliveris A, Samowitz W, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991;66:589–600.CrossRefPubMedGoogle Scholar
  14. 14.
    Reynolds AB, Herbert L, Cleveland JL, et al. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors β-catenin, plakoglobin and armadillo. Oncogene. 1992;7:2439–45.PubMedGoogle Scholar
  15. 15.
    Hatzfeld M, Kristjanssen GI, Plessmann U, et al. Band 6 protein, a major constituent of desmosomes from stratified epithelia, is a novel member of the armadillo multigene family. J Cell Sci. 1994;107:2259–70.PubMedGoogle Scholar
  16. 16.
    Muzny DM, Scherer SE, Kaul R, et al. The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006;440(7088):1194–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Braga EA, Kashuba VI, Maliukova AV, et al. New tumor suppressor genes in hot spots of human chromosome 3: new methods of identification. Mol Biol (Mosk). 2003;37(2):194–211.CrossRefGoogle Scholar
  18. 18.
    Picelli S, Vandrovcova J, Jones S, et al. Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q. BMC Cancer. 2008;8:87.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Vasioukhin V, Fuchs E. Actin dynamics and cell–cell adhesion in epithelia. Curr Opin Cell Biol. 2001;13:76–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Kobielak A, Fuchs E. α-Catenin: at the junction of intercellular adhesion and actin dynamics. Nat Rev Mol Cell Biol. 2004;5:614–25.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Mege RM, Gavard J, Lambert M. Regulation of cell–cell junctions by the cytoskeleton. Curr Opin Cell Biol. 2006;18:541–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Hwang SG, Yu SS, Ryu JH, et al. Regulation of beta-catenin signaling and maintenance of chondrocyte differentiation by ubiquitinindependent proteasomal degradation of alpha-catenin. J Biol Chem. 2005;280(13):12758–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Kolligs FT, Bommer G, Göke B. Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis. Digestion. 2002;66(3):131–44.CrossRefPubMedGoogle Scholar
  24. 24.
    Karim R, Tse G, Putti T, et al. The significance of theWnt pathway in the pathology of human cancers. Pathology. 2004;36(2):120–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Zucker S, Vacirca J. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004;23(1–2):101–17.CrossRefPubMedGoogle Scholar
  26. 26.
    Kourtidis A, Ngok SP, Anastasiadis PZ. p120 catenin: an essential regulator of cadherin stability, adhesion-induced signaling, and cancer progression. Prog Mol Biol Transl Sci. 2013;116:409–32.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Daniel JM. Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso. Biochim Biophys Acta. 2007;1773(1):59–68.CrossRefPubMedGoogle Scholar
  28. 28.
    Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev. 2007;17(1):45–51.CrossRefPubMedGoogle Scholar
  29. 29.
    Nollet F, Berx G, van Roy F. The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer. Mol Cell Biol Res Commun. 1999;2(2):77–85.CrossRefPubMedGoogle Scholar
  30. 30.
    Rolland T, Taşan M, Charloteaux B, et al. A proteome-scale map of the human interactome network. Cell. 2014;159(5):1212–26.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Guiyang Jiang
    • 1
  • Yong Zhang
    • 1
  • Xiupeng Zhang
    • 1
  • Chuifeng Fan
    • 1
  • Liang Wang
    • 1
  • Hongtao Xu
    • 1
  • Juanhan Yu
    • 1
  • Enhua Wang
    • 1
  1. 1.Department of Pathology, First Affiliated Hospital and College of Basic Medical SciencesChina Medical UniversityShenyangChina

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