Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells

Oncogene volume 23, pages 6170–6174 (2004)Cite this article

Abstract

In this report, we have demonstrated that Wnt-2 protein is overexpressed in freshly resected human non-small-cell lung cancer (NSCLC) tissues. We have also developed a monoclonal antibody against the N-terminus of human Wnt-2 protein. This monoclonal antibody induces apoptosis in human NSCLC cell lines that overexpress Wnt-2 protein. Incubation of this antibody with normal human airway cells lacking Wnt-2 expression does not induce apoptosis. Wnt-2 signaling blockade by the anti-Wnt-2 antibody is confirmed by downregulation of cytosolic β-catenin and reduction in TCF-dependent transcriptional activity (TOPFLASH assay). In addition, Wnt-2-specific small interfering RNA (siRNA) treatment in the NSCLC cell line A549 also downregulated cytosolic β-catenin and induced apoptosis. Moreover, downregulation of an inhibitor of apoptosis family protein, Survivin, was noticed both in the Wnt-2 antibody- and siRNA-treated NSCLC cells, suggesting that inhibition of Wnt-2-mediated signaling induces apoptosis through inactivating Survinin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Bienz M and Clevers H . (2000). Cell, 103, 311–320.

  • Blasband A, Schryver B and Papkoff J . (1992). Oncogene, 7, 153–161.

  • Chai J, Du C, Wu JW, Kyin S, Wang X and Shi Y . (2000). Nature, 406, 855–862.

  • Chen S, Guttridge DC, You Z, Zhang Z, Fribley A, Mayo MW, Kitajewski J and Wang CY . (2001). J. Cell Biol., 152, 87–96.

  • Dale TC, Weber-Hall SJ, Smith K, Huguet EL, Jayatilake H, Gusterson BA, Shuttleworth G, O'Hare M and Harris AL . (1996). Cancer Res., 56, 4320–4323.

  • Dann CE, Hsieh JC, Rattner A, Sharma D, Nathans J and Leahy DJ . (2001). Nature, 412, 86–90.

  • Elbashir SM, Harborth J, Weber K and Tuschl T . (2002). Methods, 26, 199–213.

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B and Kinzler KW . (1998). Science, 281, 1509–1512.

  • Holcombe RF, Marsh JL, Waterman ML, Lin F, Milovanovic T and Truong T . (2002). Mol. Pathol., 55, 220–226.

  • Hsieh JC, Rattner A, Smallwood PM and Nathans J . (1999). Proc. Natl. Acad. Sci. USA, 96, 3546–3551.

  • Huguet EL, McMahon JA, McMahon AP, Bicknell R and Harris AL . (1994). Cancer Res., 54, 2615–2621.

  • Ioannidis V, Beermann F, Clevers H and Held W . (2001). Nat. Immunol., 2, 691–697.

  • Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ and Thun MJ . (2004). CA Cancer J. Clin., 54, 8–29.

  • Katoh M . (2001). Int. J. Oncol., 19, 1003–1007.

  • Kim PJ, Plescia J, Clevers H, Fearon ER and Altieri DC . (2003). Lancet, 362, 205–209.

  • Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC and Altieri DC . (1998). Nature, 396, 580–584.

  • Minna JD, Roth JA and Gazdar AF . (2002). Cancer Cell, 1, 49–52.

  • Nusse R and Varmus HE . (1982). Cell, 31, 99–109.

  • Olie RA, Simoes-Wust AP, Baumann B, Leech SH, Fabbro D, Stahel RA and Zangemeister-Wittke U . (2000). Cancer Res., 60, 2805–2809.

  • Orford K, Orford CC and Byers SW . (1999). J. Cell Biol., 146, 855–868.

  • Peifer M and Polakis P . (2000). Science, 287, 1606–1609.

  • Pham K, Milovanovic T, Barr RJ, Truong T and Holcombe RF . (2003). Mol. Pathol., 56, 280–285.

  • Polakis P . (2000). Genes Dev., 14, 1837–1851.

  • Reya T, O'Riordan M, Okamura R, Devaney E, Willert K, Nusse R and Grosschedl R . (2000). Immunity, 13, 15–24.

  • Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y and Nakamura Y . (2000). Nat. Genet., 24, 245–250.

  • Shih IM, Yu J, He TC, Vogelstein B and Kinzler KW . (2000). Cancer Res., 60, 1671–1676.

  • Shimizu H, Julius MA, Giarre M, Zheng Z, Brown AM and Kitajewski J . (1997). Cell Growth Differ., 8, 1349–1358.

  • Smith K, Bui TD, Poulsom R, Kaklamanis L, Williams G and Harris AL . (1999). Br. J. Cancer, 81, 496–502.

  • Srinivasula SM, Datta P, Fan XJ, Fernandes-Alnemri T, Huang Z and Alnemri ES . (2000). J. Biol. Chem., 275, 36152–36157.

  • Tetsu O and McCormick F . (1999). Nature, 398, 422–426.

  • Uematsu K, Kanazawa S, You L, He B, Xu Z, Li K, Peterlin BM, McCormick F and Jablons DM . (2003). Cancer Res., 63, 4547–4551.

  • Uthoff SM, Eichenberger MR, McAuliffe TL, Hamilton CJ and Galandiuk S . (2001). Mol. Carcinog., 31, 56–62.

  • Veeman MT, Axelrod JD and Moon RT . (2003). Dev. Cell, 5, 367–377.

  • Vider BZ, Zimber A, Chastre E, Prevot S, Gespach C, Estlein D, Wolloch Y, Tronick SR, Gazit A and Yaniv A . (1996). Oncogene, 12, 153–158.

  • Wang CY, Guttridge DC, Mayo MW and Baldwin Jr AS . (1999). Mol. Cell. Biol., 19, 5923–5929.

  • Wodarz A and Nusse R . (1998). Annu. Rev. Cell Dev. Biol., 14, 59–88.

  • You Z, Saims D, Chen S, Zhang Z, Guttridge DC, Guan KL, MacDougald OA, Brown AM, Evan G, Kitajewski J and Wang CY . (2002). J. Cell Biol., 157, 429–440.

  • Zhang T, Otevrel T, Gao Z, Ehrlich SM, Fields JZ and Boman BM . (2001). Cancer Res., 61, 8664–8667.

Download references

Acknowledgements

This work was supported by the Larry Hall memorial trust and the Kazan, McClain, Edises, Abrams, Fernandez, Lyons & Farrise Foundation.

Author information

Authors and Affiliations

  1. Department of Surgery, Thoracic Oncology Laboratory, Comprehensive Cancer Center, University of California, San Francisco, 94115, CA, USA

    Liang You, Biao He, Zhidong Xu, Kazutsugu Uematsu, Julien Mazieres, Iwao Mikami, Noemi Reguart, Frank McCormick & David M Jablons

  2. Office of the Director, Center for Cancer Research, National Cancer Institute, Bethesda, 20892, MD, USA

    Terry W Moody

  3. Department of Pathology and Obstetrics and Gynecology, College of Physician and Surgeons, Columbia University, New York, 10032, NY, USA

    Jan Kitajewski

Authors
  1. Liang You
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Biao He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhidong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazutsugu Uematsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julien Mazieres
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Iwao Mikami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Noemi Reguart
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Terry W Moody
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jan Kitajewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Frank McCormick
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David M Jablons
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David M Jablons.

Rights and permissions

Reprints and permissions

About this article

Cite this article

You, L., He, B., Xu, Z. et al. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene 23, 6170–6174 (2004). https://doi.org/10.1038/sj.onc.1207844

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207844

Keywords

This article is cited by

Search

Advanced search

Quick links