Abstract
Non small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the United States and worldwide. Unfortunately, standard therapies remain inadequate. An increased understanding of the molecular biology of lung cancer biology is required to develop more effective new therapies. In this report, we show that the Wnt pathway is activated through Dishevelled (Dvl) overexpression in NSCLC. Analysis of freshly resected tumors and lung cancer cell lines demonstrate that Dvl-3, a critical mediator of Wnt signaling, is overexpressed. Specifically, Dvl-3 was overexpressed significantly in 75% of fresh NSCLC microdissected samples compared to control paired matched normal lung samples. To evaluate the biological significance of Wnt signaling and, in particular, Dvl function in lung cancer, we transfected siRNA (designed to inhibit selectively human Dvl-1, -2, and -3), to the NSCLC cell line H1703, which is known to have β-catenin-mediated Tcf-dependent transcriptional activity. Here, we demonstrate that Dvl-specific siRNA treatment in H1703 decreases significantly Dvl and β-catenin expression, resulting in reduction of Tcf-dependent transcriptional activity, and, importantly, growth inhibition. Taken together, these data support the novel hypothesis that Dvl overexpression is critical to Wnt signaling activation and cell growth in NSCLC.
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References
Brantjes H, Barker N, van Es J and Clevers H . (2002). Biol. Chem., 383, 255–261.
Brognard J and Dennis PA . (2002). Cell Death Differ., 9, 893–904.
Cagatay T and Ozturk M . (2002). Oncogene, 21, 7971–7980.
Hommura F, Furuuchi K, Yamazaki K, Ogura S, Kinoshita I, Shimizu M, Moriuchi T, Katoh H, Nishimura M and Dosaka-Akita H . (2002). Cancer, 94, 752–758.
Li L, Mao J, Sun L, Liu W and Wu D . (2002). J. Biol. Chem., 277, 5977–5981.
Liu J, Stevens J, Rote CA, Yost HJ, Hu Y, Neufeld KL, White RL and Matsunami N . (2001). Mol. Cell, 7, 927–936.
Matsuzawa SI and Reed JC . (2001). Mol. Cell, 7, 915–926.
Minna JD . (1998). Harrison's Principles of Internal Medicine Vol. 14. Fauci AS, Braunwald E, Isselbacher KJ, Martin JB (eds). McGraw-Hill: New York, pp. 522–562.
Morin PJ . (1999). BioEssays, 21, 1021–1030.
Polakis P . (2000). Genes Dev., 14, 1837–1851.
Sekido Y, Fong KM and Minna JD . (1998). Biochim. Biophys. Acta, 1378, F21–F59.
Shimizu H, Julius MA, Giarre M, Zheng Z, Brown AM and Kitajewski J . (1997). Cell Growth Differ., 8, 1349–1358.
Sunaga N, Kohno T, Kolligs FT, Fearon ER, Saito R and Yokota J . (2001). Genes Chromosom. Cancer, 30, 316–321.
Ueda M, Gemmill RM, West J, Winn R, Sugita M, Tanaka N, Ueki M and Drabkin HA . (2001). Br. J. Cancer, 85, 64–68.
Wang J, Shou J and Chen X . (2000). Oncogene, 19, 1843–1848.
Wharton Jr KA . (2003). Dev. Biol., 253, 1–17.
Winn RA, Bremnes RM, Bemis L, Franklin WA, Miller YE, Cool C and Heasley LE . (2002). Oncogene, 21, 7497–7506.
You L, Uematsu K, McBrine MJ, McCormick F and Jablons DM . (2001). Proc. Am. Assoc. Cancer Res., 42, 609.
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Uematsu, K., He, B., You, L. et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene 22, 7218–7221 (2003). https://doi.org/10.1038/sj.onc.1206817
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DOI: https://doi.org/10.1038/sj.onc.1206817
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