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Stem Cells and Lung Cancer

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Stem Cells and Cancer

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Abstract

Lung cancer with its more than 1 million deaths per year is the leading cause of cancer mortality for both men and women worldwide. Despite recent advances in current treatment modalities, overall survival rates have hardly improved. Overall 5-year lung cancer survival rate is approximately 15% in the USA and these numbers are much lower in the developing world. The intrinsic resistance shown by stem/progenitor cells following traditional chemotherapy leads to disease recurrence and decreased patient survival and is a major clinical challenge to overcome. Populations of cancer stem cells (CSCs) have been found and characterized in multiple malignancies such as many hematological, breast, colorectal, brain, pancreatic, and maxillofacial cancers; however, this has not fully happened yet in human lung cancer, making such a task a paramount necessity. In this chapter we explore the roles of the main developmental signaling pathways in lung organogenesis and maintenance, together with the issue of homeostatic pulmonary stem cells within specific ‘niches’ in the bronchopulmonary tree. We explain how aberrations inflicted in many of the components of this complex homeostatic machine can lead to the formation of lung cancer stem cells with accumulated permanent mutations that allow them to repopulate their tumors rendering these lesions resistant to traditional cytotoxic treatments, resulting in dismal prognosis and poor survival rates. The aim, of course is to ultimately integrate the knowledge of these mechanisms into tangible tools that can be eventually translated into novel therapies for lung cancer.

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References

  • Akiyama, T., Wnt/beta-catenin signaling. Cytokine Growth Factor Rev, 2000. 11(4): 273–82.

    PubMed  CAS  Google Scholar 

  • Akiyoshi, T., et al., Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation. Gut, 2006. 55(7): 991–9.

    PubMed  CAS  Google Scholar 

  • Al-Hajj, M., et al., Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003. 100(7): 3983–8.

    PubMed  CAS  Google Scholar 

  • Al-Hajj, M., et al., Therapeutic implications of cancer stem cells. Curr Opin Genet Dev, 2004. 14(1): 43–7.

    PubMed  CAS  Google Scholar 

  • Altundag, O., et al., Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a Phase II clinical trial. Cancer, 2005. 104(9): 2033–4; author reply 2034.

    PubMed  Google Scholar 

  • Aulehla, A. and B. G. Herrmann, Segmentation in vertebrates: clock and gradient finally joined. Genes Dev, 2004. 18(17): 2060–7.

    PubMed  CAS  Google Scholar 

  • Aulehla, A., et al., Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev Cell, 2003. 4(3): 395–406.

    PubMed  CAS  Google Scholar 

  • Aza-Blanc, P., et al., Proteolysis that is inhibited by hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor. Cell, 1997. 89(7): 1043–53.

    PubMed  CAS  Google Scholar 

  • Ball, D.W., et al., Identification of a human achaete-scute homolog highly expressed in neuroendocrine tumors. Proc Natl Acad Sci USA, 1993. 90(12): 5648–52.

    PubMed  CAS  Google Scholar 

  • Banziger, C., et al., Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell, 2006. 125(3): 509–22.

    PubMed  CAS  Google Scholar 

  • Barolo, S. and J. W. Posakony, Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev, 2002. 16(10): 1167–81.

    PubMed  CAS  Google Scholar 

  • Barrandon, Y., et al., Restoration of growth potential in paraclones of human keratinocytes by a viral oncogene. Proc Natl Acad Sci USA, 1989. 86(11): 4102–6.

    PubMed  CAS  Google Scholar 

  • Bartscherer, K., et al., Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell, 2006. 125(3): 523–33.

    PubMed  CAS  Google Scholar 

  • Batlle, E., et al., Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell, 2002. 111(2): 251–63.

    PubMed  CAS  Google Scholar 

  • Beachy, P.A., S. S. Karhadkar, and D. M. Berman, Tissue repair and stem cell renewal in carcinogenesis. Nature, 2004. 432(7015): 324–31.

    PubMed  CAS  Google Scholar 

  • Beier, D., et al., CD133(+) and CD133(–) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res, 2007. 67(9): 4010–5.

    PubMed  CAS  Google Scholar 

  • Bellusci, S., et al., Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development, 1997. 124(1): 53–63.

    PubMed  CAS  Google Scholar 

  • Benitah, S.A., et al., Stem cell depletion through epidermal deletion of Rac1. Science, 2005. 309(5736): 933–5.

    PubMed  Google Scholar 

  • Bergsagel, D.E. and F. A. Valeriote, Growth characteristics of a mouse plasma cell tumor. Cancer Res, 1968. 28(11): 2187–96.

    PubMed  CAS  Google Scholar 

  • Berman, D.M., et al., Medulloblastoma growth inhibition by hedgehog pathway blockade. Science, 2002. 297(5586): 1559–61.

    PubMed  CAS  Google Scholar 

  • Berman, D.M., et al., Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature, 2003. 425(6960): 846–51.

    PubMed  CAS  Google Scholar 

  • Berns, A., Stem cells for lung cancer? Cell, 2005. 121(6): 811–3.

    PubMed  CAS  Google Scholar 

  • Bettenhausen, B., et al., Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Development, 1995. 121(8): 2407–18.

    PubMed  CAS  Google Scholar 

  • Bhanot, P., et al., A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature, 1996. 382(6588): 225–30.

    PubMed  CAS  Google Scholar 

  • Bitgood, M.J. and A. P. McMahon, Hedgehog and Bmp genes are coexpressed at many diverse sites of cell–cell interaction in the mouse embryo. Dev Biol, 1995. 172(1): 126–38.

    PubMed  CAS  Google Scholar 

  • Bixby, S., et al., Cell-intrinsic differences between stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity. Neuron, 2002. 35(4): 643–56.

    PubMed  CAS  Google Scholar 

  • Blair, A., et al., Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood, 1997. 89(9): 3104–12.

    PubMed  CAS  Google Scholar 

  • Bonnet, D. and J. E. Dick, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med, 1997. 3(7): 730–7.

    PubMed  CAS  Google Scholar 

  • Bottinger, E.P., et al., Transgenic mice overexpressing a dominant-negative mutant type II transforming growth factor beta receptor show enhanced tumorigenesis in the mammary gland and lung in response to the carcinogen 7,12-dimethylbenz-[a]-anthracene. Cancer Res, 1997. 57(24): 5564–70.

    PubMed  CAS  Google Scholar 

  • Bray, S.J., Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol, 2006. 7(9): 678–89.

    PubMed  CAS  Google Scholar 

  • Bruce, W.R. and H. Van Der Gaag, A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature, 1963. 199: 79–80.

    PubMed  CAS  Google Scholar 

  • Calvi, L.M., et al., Osteoblastic cells regulate the haematopoietic stem cell niche. Nature, 2003. 425(6960): 841–6.

    PubMed  CAS  Google Scholar 

  • Carney, D.N., et al., Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients. Stem Cells, 1982. 1(3): 149–64.

    PubMed  CAS  Google Scholar 

  • Cavallo, R.A., et al., Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature, 1998. 395(6702): 604–8.

    PubMed  CAS  Google Scholar 

  • Chepko, G. and R. B. Dickson, Ultrastructure of the putative stem cell niche in rat mammary epithelium. Tissue Cell, 2003. 35(2): 83–93.

    PubMed  CAS  Google Scholar 

  • Chen, H., et al., Conservation of the Drosophila lateral inhibition pathway in human lung cancer: a hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression. Proc Natl Acad Sci USA, 1997. 94(10): 5355–60.

    PubMed  CAS  Google Scholar 

  • Chen, G., et al., A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development. Genes Dev, 1999a. 13(17): 2218–30.

    PubMed  CAS  Google Scholar 

  • Chen, C.H., et al., Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell, 1999b. 98(3): 305–16.

    PubMed  CAS  Google Scholar 

  • Chen, A.E., D. D. Ginty, and C. M. Fan, Protein kinase A signalling via CREB controls myogenesis induced by Wnt proteins. Nature, 2005. 433(7023): 317–22.

    PubMed  CAS  Google Scholar 

  • Cheng, Y.C., et al., Notch activation regulates the segregation and differentiation of rhombomere boundary cells in the zebrafish hindbrain. Dev Cell, 2004. 6(4): 539–50.

    PubMed  CAS  Google Scholar 

  • Chung, E.J., et al., Regulation of leukemic cell adhesion, proliferation, and survival by beta-catenin. Blood, 2002. 100(3): 982–90.

    PubMed  CAS  Google Scholar 

  • Collins, B.J., W. Kleeberger, and D. W. Ball, Notch in lung development and lung cancer. Semin Cancer Biol, 2004. 14(5): 357–64.

    PubMed  CAS  Google Scholar 

  • Cooper, M.K., et al., Teratogen-mediated inhibition of target tissue response to Shh signaling. Science, 1998. 280(5369): 1603–7.

    PubMed  CAS  Google Scholar 

  • Couso, J.P. and A. Martinez Arias, Notch is required for wingless signaling in the epidermis of Drosophila. Cell, 1994. 79(2): 259–72.

    PubMed  CAS  Google Scholar 

  • Crittenden, S.L., et al., A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature, 2002. 417(6889): 660–3.

    PubMed  CAS  Google Scholar 

  • Cui, H., Y. Meng, and R. F. Bulleit, Inhibition of glycogen synthase kinase 3beta activity regulates proliferation of cultured cerebellar granule cells. Brain Res Dev Brain Res, 1998. 111(2): 177–88.

    PubMed  CAS  Google Scholar 

  • Dalerba, P., et al., Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A, 2007. 104(24): 10158–63.

    PubMed  CAS  Google Scholar 

  • Dang, T.P., et al., Chromosome 19 translocation, overexpression of Notch3, and human lung cancer. J Natl Cancer Inst, 2000. 92(16): 1355–7.

    PubMed  CAS  Google Scholar 

  • Davidson, E.H. and D. H. Erwin, Gene regulatory networks and the evolution of animal body plans. Science, 2006. 311(5762): 796–800.

    PubMed  CAS  Google Scholar 

  • De Langhe, S.P., et al., Dickkopf-1 (DKK1) reveals that fibronectin is a major target of Wnt signaling in branching morphogenesis of the mouse embryonic lung. Dev Biol, 2005. 277(2): 316–31.

    PubMed  Google Scholar 

  • DeMayo, F.J., et al., Expression of SV40 T antigen under control of rabbit uteroglobin promoter in transgenic mice. Am J Physiol, 1991. 261(2 Pt 1): L70–6.

    PubMed  CAS  Google Scholar 

  • Denef, N., et al., Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened. Cell, 2000. 102(4): 521–31.

    PubMed  CAS  Google Scholar 

  • Derksen, P.W., et al., Illegitimate WNT signaling promotes proliferation of multiple myeloma cells. Proc Natl Acad Sci USA, 2004. 101(16): 6122–7.

    PubMed  CAS  Google Scholar 

  • Desai, B., M. J. Rogers, and M. A. Chellaiah, Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells. Mol Cancer, 2007. 6: 18.

    PubMed  Google Scholar 

  • Diaz-Benjumea, F.J. and S. M. Cohen, Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development, 1995. 121(12): 4215–25.

    PubMed  CAS  Google Scholar 

  • Donjacour, A.A. and G. R. Cunha, Stromal regulation of epithelial function. Cancer Treat Res, 1991. 53: 335–64.

    PubMed  CAS  Google Scholar 

  • Dy, G.K., et al., A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study. Ann Oncol, 2005. 16(11): 1811–6.

    PubMed  CAS  Google Scholar 

  • Ehebauer, M.T., et al., High-resolution crystal structure of the human Notch 1 ankyrin domain. Biochem J, 2005. 392(Pt 1): 13–20.

    PubMed  CAS  Google Scholar 

  • Ehebauer, M., P. Hayward, and A. M. Arias, Notch, a universal arbiter of cell fate decisions. Science, 2006. 314(5804): 1414–5.

    PubMed  CAS  Google Scholar 

  • Eramo, A., et al., Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ, 2008. 15(3): 504–14.

    PubMed  CAS  Google Scholar 

  • Estrach, S., et al., Jagged 1 is a beta-catenin target gene required for ectopic hair follicle formation in adult epidermis. Development, 2006. 133(22): 4427–38.

    PubMed  CAS  Google Scholar 

  • Fedi, P., et al., Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. J Biol Chem, 1999. 274(27): 19465–72.

    PubMed  CAS  Google Scholar 

  • Fisher, G.H., et al., Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev, 2001. 15(24): 3249–62.

    PubMed  CAS  Google Scholar 

  • Franklin, W.A., et al., Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis. J Clin Invest, 1997. 100(8): 2133–7.

    PubMed  CAS  Google Scholar 

  • Freeman, M., Feedback control of intercellular signalling in development. Nature, 2000. 408(6810): 313–9.

    PubMed  CAS  Google Scholar 

  • Galceran, J., et al., LEF1-mediated regulation of Delta-like1 links Wnt and Notch signaling in somitogenesis. Genes Dev, 2004. 18(22): 2718–23.

    PubMed  CAS  Google Scholar 

  • Galli, R., et al., Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res, 2004. 64(19): 7011–21.

    PubMed  CAS  Google Scholar 

  • Garcion, E., et al., Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development, 2004. 131(14): 3423–32.

    PubMed  CAS  Google Scholar 

  • Giangreco, A., et al., Molecular phenotype of airway side population cells. Am J Physiol Lung Cell Mol Physiol, 2004. 286(4): L624–30.

    PubMed  CAS  Google Scholar 

  • Giangreco, A., K. R. Groot, and S. M. Janes, Lung cancer and lung stem cells: strange bedfellows? Am J Respir Crit Care Med, 2007. 175(6): 547–53.

    PubMed  Google Scholar 

  • Goodell, M.A., et al., Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med, 1996. 183(4): 1797–806.

    PubMed  CAS  Google Scholar 

  • Goodrich, L.V. and M. P. Scott, Hedgehog and patched in neural development and disease. Neuron, 1998. 21(6): 1243–57.

    PubMed  CAS  Google Scholar 

  • Goodrich, L.V., et al., Altered neural cell fates and medulloblastoma in mouse patched mutants. Science, 1997. 277(5329): 1109–13.

    PubMed  CAS  Google Scholar 

  • Gregorieff, A. and H. Clevers, Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev, 2005. 19(8): 877–90.

    PubMed  CAS  Google Scholar 

  • Gross, D.J., et al., The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R. Endocr Relat Cancer, 2006. 13(2): 535–40.

    PubMed  CAS  Google Scholar 

  • Guerra, C., et al., Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell, 2003. 4(2): 111–20.

    PubMed  CAS  Google Scholar 

  • Gutova, M., et al., Identification of uPAR-positive chemoresistant cells in small cell lung cancer. PLoS ONE, 2007. 2(2): e243.

    PubMed  Google Scholar 

  • He, B., et al., Wnt signaling in stem cells and non-small-cell lung cancer. Clin Lung Cancer, 2005. 7(1): 54–60.

    PubMed  CAS  Google Scholar 

  • Heemskerk, J. and S. DiNardo, Drosophila hedgehog acts as a morphogen in cellular patterning. Cell, 1994. 76(3): 449–60.

    PubMed  CAS  Google Scholar 

  • Hemmati, H.D., et al., Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA, 2003. 100(25): 15178–83.

    PubMed  CAS  Google Scholar 

  • Hibi, K., et al., Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer. Oncogene, 1991. 6(12): 2291–6.

    PubMed  CAS  Google Scholar 

  • Hing, H.K., X. Sun, and S. Artavanis-Tsakonas, Modulation of wingless signaling by Notch in Drosophila. Mech Dev, 1994. 47(3): 261–8.

    PubMed  CAS  Google Scholar 

  • Hirschmann-Jax, C., et al., A distinct “side population” of cells in human tumor cells: implications for tumor biology and therapy. Cell Cycle, 2005. 4(2): 203–5.

    PubMed  CAS  Google Scholar 

  • Ho, M.M., et al., Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res, 2007. 67(10): 4827–33.

    PubMed  CAS  Google Scholar 

  • Hoang, B.H., et al., Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma. Int J Cancer, 2004a. 109(1): 106–11.

    PubMed  CAS  Google Scholar 

  • Hoang, B.H., et al., Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway. Cancer Res, 2004b. 64(8): 2734–9.

    PubMed  CAS  Google Scholar 

  • Hochedlinger, K., et al., Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell, 2005. 121(3): 465–77.

    PubMed  CAS  Google Scholar 

  • Hofmann, K., A superfamily of membrane-bound O-acyltransferases with implications for wnt signaling. Trends Biochem Sci, 2000. 25(3): 111–2.

    PubMed  CAS  Google Scholar 

  • Hong, K.U., et al., Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am J Respir Cell Mol Biol, 2001. 24(6): 671–81.

    PubMed  CAS  Google Scholar 

  • Hooper, J.E. and M. P. Scott, Communicating with Hedgehogs. Nat Rev Mol Cell Biol, 2005. 6(4): 306–17.

    PubMed  CAS  Google Scholar 

  • Houghton, J., et al., Stem cells and cancer. Semin Cancer Biol, 2007. 17(3): 191–203.

    PubMed  CAS  Google Scholar 

  • Hsieh, J.C., et al., A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature, 1999. 398(6726): 431–6.

    PubMed  CAS  Google Scholar 

  • Ingham, P.W., Transducing Hedgehog: the story so far. EMBO J, 1998. 17(13): 3505–11.

    PubMed  CAS  Google Scholar 

  • Iwatsuki, K., et al., Wnt signaling interacts with Shh to regulate taste papilla development. Proc Natl Acad Sci USA, 2007. 104(7): 2253–8.

    PubMed  CAS  Google Scholar 

  • Jackson, E.L., et al., Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev, 2001. 15(24): 3243–8.

    PubMed  CAS  Google Scholar 

  • Jaekel, R. and T. Klein, The Drosophila Notch inhibitor and tumor suppressor gene lethal (2) giant discs encodes a conserved regulator of endosomal trafficking. Dev Cell, 2006. 11(5): 655–69.

    PubMed  CAS  Google Scholar 

  • Jemal, A., et al., Cancer statistics, 2007. CA Cancer J Clin, 2007. 57(1): 43–66.

    PubMed  Google Scholar 

  • Jensen, U.B., S. Lowell, and F. M. Watt, The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labelling and lineage analysis. Development, 1999. 126(11): 2409–18.

    PubMed  CAS  Google Scholar 

  • Jhappan, C., et al., Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev, 1992. 6(3): 345–55.

    PubMed  CAS  Google Scholar 

  • Ji, H., et al., The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell, 2006. 9(6): 485–95.

    PubMed  CAS  Google Scholar 

  • Johnson, L., et al., Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature, 2001. 410(6832): 1111–6.

    PubMed  CAS  Google Scholar 

  • Jones, S.E. and C. Jomary, Secreted Frizzled-related proteins: searching for relationships and patterns. Bioessays, 2002. 24(9): 811–20.

    PubMed  CAS  Google Scholar 

  • Jones, P.H. and F. M. Watt, Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell, 1993. 73(4): 713–24.

    PubMed  CAS  Google Scholar 

  • Juopperi, T.A., et al., Isolation of bone marrow-derived stem cells using density-gradient separation. Exp Hematol, 2007. 35(2): 335–41.

    PubMed  CAS  Google Scholar 

  • Kalderon, D., Transducing the hedgehog signal. Cell, 2000. 103(3): 371–4.

    PubMed  CAS  Google Scholar 

  • Kiel, M.J., et al., SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell, 2005. 121(7): 1109–21.

    PubMed  CAS  Google Scholar 

  • Kiger, A.A., H. White-Cooper, and M. T. Fuller, Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature, 2000. 407(6805): 750–4.

    PubMed  CAS  Google Scholar 

  • Kim, C.F., et al., Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell, 2005. 121(6): 823–35.

    PubMed  CAS  Google Scholar 

  • Kim, J., et al., Wnt inhibitory factor inhibits lung cancer cell growth. J Thorac Cardiovasc Surg, 2007. 133(3): 733–7.

    PubMed  CAS  Google Scholar 

  • Kondo, T., T. Setoguchi, and T. Taga, Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA, 2004. 101(3): 781–6.

    PubMed  CAS  Google Scholar 

  • Kopan, R., Notch: a membrane-bound transcription factor. J Cell Sci, 2002. 115(Pt 6): 1095–7.

    PubMed  CAS  Google Scholar 

  • Korinek, V., et al., Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet, 1998. 19(4): 379–83.

    PubMed  CAS  Google Scholar 

  • Kramps, T., et al., Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell, 2002. 109(1): 47–60.

    PubMed  CAS  Google Scholar 

  • Krieghoff, E., J. Behrens, and B. Mayr, Nucleo-cytoplasmic distribution of beta-catenin is regulated by retention. J Cell Sci, 2006. 119(Pt 7): 1453–63.

    PubMed  CAS  Google Scholar 

  • Lai, K., et al., Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci, 2003. 6(1): 21–7.

    PubMed  CAS  Google Scholar 

  • Lako, M., et al., Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung. Gene, 1998. 219(1–2): 101–10.

    PubMed  CAS  Google Scholar 

  • Lapidot, T., et al., A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 1994. 367(6464): 645–8.

    PubMed  CAS  Google Scholar 

  • Le, Q.T., et al., An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res, 2006. 12(5): 1507–14.

    PubMed  CAS  Google Scholar 

  • Lee, J.J., et al., Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell, 1992. 71(1): 33–50.

    PubMed  CAS  Google Scholar 

  • Lee, A.Y., et al., Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma. Oncogene, 2004. 23(39): 6672–6.

    PubMed  CAS  Google Scholar 

  • Lee, L.N., et al., CD44 splicing pattern is associated with disease progression in pulmonary adenocarcinoma. J Formos Med Assoc, 2005. 104(8): 541–8.

    PubMed  CAS  Google Scholar 

  • Le Borgne, R., Regulation of Notch signalling by endocytosis and endosomal sorting. Curr Opin Cell Biol, 2006. 18(2): 213–22.

    PubMed  CAS  Google Scholar 

  • Li, C., et al., Wnt5a participates in distal lung morphogenesis. Dev Biol, 2002. 248(1): 68–81.

    PubMed  CAS  Google Scholar 

  • Li, C., et al., Identification of pancreatic cancer stem cells. Cancer Res, 2007. 67(3): 1030–7.

    PubMed  CAS  Google Scholar 

  • Lin, X., Functions of heparan sulfate proteoglycans in cell signaling during development. Development, 2004. 131(24): 6009–21.

    PubMed  CAS  Google Scholar 

  • Linnoila, R.I., et al., Morphometric analysis of CC10-hASH1 transgenic mouse lung: a model for bronchiolization of alveoli and neuroendocrine carcinoma. Exp Lung Res, 2000. 26(8): 595–615.

    PubMed  CAS  Google Scholar 

  • Linnoila, R.I., et al., Mouse lung neuroendocrine carcinomas: distinct morphologies, same transcription factors. Exp Lung Res, 2005. 31(1): 37–55.

    PubMed  CAS  Google Scholar 

  • Litingtung, Y., et al., Sonic hedgehog is essential to foregut development. Nat Genet, 1998. 20(1): 58–61.

    PubMed  CAS  Google Scholar 

  • Liu, J. and G. Jiang, CD44 and hematologic malignancies. Cell Mol Immunol, 2006. 3(5): 359–65.

    PubMed  CAS  Google Scholar 

  • Liu, T., et al., G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway. Science, 2001. 292(5522): 1718–22.

    PubMed  CAS  Google Scholar 

  • Liu, H., et al., Predicting survival within the lung cancer histopathological hierarchy using a multi-scale genomic model of development. PLoS Med, 2006. 3(7): e232.

    PubMed  Google Scholar 

  • Lo Celso, C., D. M. Prowse, and F. M. Watt, Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development, 2004. 131(8): 1787–99.

    PubMed  CAS  Google Scholar 

  • Logan, C.Y. and R. Nusse, The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol, 2004. 20: 781–810.

    PubMed  CAS  Google Scholar 

  • Lowry, W.E. and L. Richter, Signaling in adult stem cells. Front Biosci, 2007. 12: 3911–27.

    PubMed  CAS  Google Scholar 

  • Lu, W., et al., Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell, 2004. 119(1): 97–108.

    PubMed  CAS  Google Scholar 

  • Martinez Arias, A. and A. Stewart, Molecular Principles of Animal Development. 2002, New York: Oxford University Press.

    Google Scholar 

  • McMahon, A.P., More surprises in the Hedgehog signaling pathway. Cell, 2000. 100(2): 185–8.

    PubMed  CAS  Google Scholar 

  • McMahon, A.P., P. W. Ingham, and C. J. Tabin, Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol, 2003. 53: 1–114.

    PubMed  CAS  Google Scholar 

  • Meuwissen, R. and A. Berns, Mouse models for human lung cancer. Genes Dev, 2005. 19(6): 643–64.

    PubMed  CAS  Google Scholar 

  • Meuwissen, R., et al., Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene. Oncogene, 2001. 20(45): 6551–8.

    PubMed  CAS  Google Scholar 

  • Meuwissen, R., et al., Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell, 2003. 4(3): 181–9.

    PubMed  CAS  Google Scholar 

  • Mikels, A.J. and R. Nusse, Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol, 2006. 4(4): e115.

    PubMed  Google Scholar 

  • Miller, J.R., The Wnts. Genome Biol, 2002. 3(1): REVIEWS3001.

    Google Scholar 

  • Miller, L.A., S. E. Wert, and J. A. Whitsett, Immunolocalization of sonic hedgehog (Shh) in developing mouse lung. J Histochem Cytochem, 2001. 49(12): 1593–604.

    PubMed  CAS  Google Scholar 

  • Minna, J.D., J. M. Kurie, and T. Jacks, A big step in the study of small cell lung cancer. Cancer Cell, 2003. 4(3): 163–6.

    PubMed  CAS  Google Scholar 

  • Moberg, K.H., et al., Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev Cell, 2005. 9(5): 699–710.

    PubMed  CAS  Google Scholar 

  • Muller, A., et al., Involvement of chemokine receptors in breast cancer metastasis. Nature, 2001. 410(6824): 50–6.

    PubMed  CAS  Google Scholar 

  • Nam, Y., et al., Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex. J Biol Chem, 2003. 278(23): 21232–9.

    PubMed  CAS  Google Scholar 

  • Nam, Y., et al., Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell, 2006. 124(5): 973–83.

    PubMed  CAS  Google Scholar 

  • Naor, D., et al., CD44 in cancer. Crit Rev Clin Lab Sci, 2002. 39(6): 527–79.

    PubMed  CAS  Google Scholar 

  • Neumann, C.J. and S. M. Cohen, A hierarchy of cross-regulation involving Notch, wingless, vestigial and cut organizes the dorsal/ventral axis of the Drosophila wing. Development, 1996. 122(11): 3477–85.

    PubMed  CAS  Google Scholar 

  • Newman-Smith, E.D. and J. H. Rothman, The maternal-to-zygotic transition in embryonic patterning of Caenorhabditis elegans. Curr Opin Genet Dev, 1998. 8(4): 472–80.

    PubMed  CAS  Google Scholar 

  • Nishimaki, H., et al., A role of activated Sonic hedgehog signaling for the cellular proliferation of oral squamous cell carcinoma cell line. Biochem Biophys Res Commun, 2004. 314(2): 313–20.

    PubMed  CAS  Google Scholar 

  • Noramly, S., A. Freeman, and B. A. Morgan, beta-Catenin signaling can initiate feather bud development. Development, 1999. 126(16): 3509–21.

    PubMed  CAS  Google Scholar 

  • Nusse, R., Cell biology: relays at the membrane. Nature, 2005. 438(7069): 747–9.

    PubMed  CAS  Google Scholar 

  • O'Brien, C.A., et al., A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 2007. 445(7123): 106–10.

    PubMed  Google Scholar 

  • Ohta, M., et al., Suppression of hematopoietic activity in tenascin-C-deficient mice. Blood, 1998. 91(11): 4074–83.

    PubMed  CAS  Google Scholar 

  • Oishi, I., et al., The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells, 2003. 8(7): 645–54.

    PubMed  CAS  Google Scholar 

  • Owens, D.M. and F. M. Watt, Contribution of stem cells and differentiated cells to epidermal tumours. Nat Rev Cancer, 2003. 3(6): 444–51.

    PubMed  CAS  Google Scholar 

  • Palmer, T.D., A. R. Willhoite, and F. H. Gage, Vascular niche for adult hippocampal neurogenesis. J Comp Neurol, 2000. 425(4): 479–94.

    PubMed  CAS  Google Scholar 

  • Pardal, R., M. F. Clarke, and S. J. Morrison, Applying the principles of stem-cell biology to cancer. Nat Rev Cancer, 2003. 3(12): 895–902.

    PubMed  CAS  Google Scholar 

  • Park, C.H., D. E. Bergsagel, and E. A. McCulloch, Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst, 1971. 46(2): 411–22.

    PubMed  CAS  Google Scholar 

  • Parkin, D.M., et al., Global cancer statistics, 2002. CA Cancer J Clin, 2005. 55(2): 74–108.

    PubMed  Google Scholar 

  • Passegue, E., et al., Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci USA, 2003. 100 Suppl 1: 11842–9.

    PubMed  Google Scholar 

  • Patrawala, L., et al., Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2– cancer cells are similarly tumorigenic. Cancer Res, 2005. 65(14): 6207–19.

    PubMed  CAS  Google Scholar 

  • Pear, W.S., et al., Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp Med, 1996. 183(5): 2283–91.

    PubMed  CAS  Google Scholar 

  • Pelengaris, S., et al., Reversible activation of c-Myc in skin: induction of a complex neoplastic phenotype by a single oncogenic lesion. Mol Cell, 1999. 3(5): 565–77.

    PubMed  CAS  Google Scholar 

  • Pelosi, G., et al., CD117 immunoreactivity in stage I adenocarcinoma and squamous cell carcinoma of the lung: relevance to prognosis in a subset of adenocarcinoma patients. Mod Pathol, 2004. 17(6): 711–21.

    PubMed  Google Scholar 

  • Pepinsky, R.B., et al., Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem, 1998. 273(22): 14037–45.

    PubMed  CAS  Google Scholar 

  • Pietsch, T., et al., Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res, 1997. 57(11): 2085–8.

    PubMed  CAS  Google Scholar 

  • Platzer, U. and H. P. Meinzer, Genetic networks in the early development of Caenorhabditis elegans. Int Rev Cytol, 2004. 234: 47–100.

    PubMed  CAS  Google Scholar 

  • Politi, K., et al., Lung adenocarcinomas induced in mice by mutant EGF receptors found in human lung cancers respond to a tyrosine kinase inhibitor or to down-regulation of the receptors. Genes Dev, 2006. 20(11): 1496–510.

    PubMed  CAS  Google Scholar 

  • Porter, J.A., K. E. Young, and P. A. Beachy, Cholesterol modification of hedgehog signaling proteins in animal development. Science, 1996. 274(5285): 255–9.

    PubMed  CAS  Google Scholar 

  • Post, L.C., M. Ternet, and B. L. Hogan, Notch/Delta expression in the developing mouse lung. Mech Dev, 2000. 98(1–2): 95–8.

    PubMed  CAS  Google Scholar 

  • Pourquie, O., The segmentation clock: converting embryonic time into spatial pattern. Science, 2003. 301(5631): 328–30.

    PubMed  CAS  Google Scholar 

  • Prince, M.E., et al., Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA, 2007. 104(3): 973–8.

    PubMed  CAS  Google Scholar 

  • Qiang, Y.W., et al., Wnt signaling in B-cell neoplasia. Oncogene, 2003. 22(10): 1536–45.

    PubMed  CAS  Google Scholar 

  • Raffel, C., et al., Sporadic medulloblastomas contain PTCH mutations. Cancer Res, 1997. 57(5): 842–5.

    PubMed  CAS  Google Scholar 

  • Rawlins, E.L. and B. L. Hogan, Epithelial stem cells of the lung: privileged few or opportunities for many? Development, 2006. 133(13): 2455–65.

    PubMed  CAS  Google Scholar 

  • Reddy, S., et al., Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech Dev, 2001. 107(1–2): 69–82.

    PubMed  CAS  Google Scholar 

  • Reya, T., et al., Stem cells, cancer, and cancer stem cells. Nature, 2001. 414(6859): 105–11.

    PubMed  CAS  Google Scholar 

  • Reya, T., et al., A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature, 2003. 423(6938): 409–14.

    PubMed  CAS  Google Scholar 

  • Reynolds, S.D., et al., Conditional clara cell ablation reveals a self-renewing progenitor function of pulmonary neuroendocrine cells. Am J Physiol Lung Cell Mol Physiol, 2000a. 278(6): L1256–63.

    PubMed  CAS  Google Scholar 

  • Reynolds, S.D., et al., Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol, 2000b. 156(1): 269–78.

    PubMed  CAS  Google Scholar 

  • Ricci-Vitiani, L., et al., Identification and expansion of human colon-cancer-initiating cells. Nature, 2007. 445(7123): 111–5.

    PubMed  CAS  Google Scholar 

  • Rijsewijk, F., et al., The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell, 1987. 50(4): 649–57.

    PubMed  CAS  Google Scholar 

  • Robbins, D.J., et al., Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. Cell, 1997. 90(2): 225–34.

    PubMed  CAS  Google Scholar 

  • Romer, J., B. S. Nielsen, and M. Ploug, The urokinase receptor as a potential target in cancer therapy. Curr Pharm Des, 2004. 10(19): 2359–76.

    PubMed  CAS  Google Scholar 

  • Rose, L.S. and K. J. Kemphues, Early patterning of the C. elegans embryo. Annu Rev Genet, 1998. 32: 521–45.

    PubMed  CAS  Google Scholar 

  • Ruiz i Altaba, A., P. Sanchez, and N. Dahmane, Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer, 2002. 2(5): 361–72.

    PubMed  CAS  Google Scholar 

  • Sampietro, J., et al., Crystal structure of a beta-catenin/BCL9/Tcf4 complex. Mol Cell, 2006. 24(2): 293–300.

    PubMed  CAS  Google Scholar 

  • Sell, S., Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol, 2004. 51(1): 1–28.

    PubMed  Google Scholar 

  • Shmelkov, S.V., et al., AC133/CD133/Prominin-1. Int J Biochem Cell Biol, 2005. 37(4): 715–9.

    PubMed  CAS  Google Scholar 

  • Shu, W., et al., Wnt7b regulates mesenchymal proliferation and vascular development in the lung. Development, 2002. 129(20): 4831–42.

    PubMed  CAS  Google Scholar 

  • Singh, S.K., et al., Identification of human brain tumour initiating cells. Nature, 2004. 432(7015): 396–401.

    PubMed  CAS  Google Scholar 

  • Silva-Vargas, V., et al., Beta-catenin and Hedgehog signal strength can specify number and location of hair follicles in adult epidermis without recruitment of bulge stem cells. Dev Cell, 2005. 9(1): 121–31.

    PubMed  CAS  Google Scholar 

  • Silver, S.J. and I. Rebay, Signaling circuitries in development: insights from the retinal determination gene network. Development, 2005. 132(1): 3–13.

    PubMed  CAS  Google Scholar 

  • Sogabe, Y., et al., Epigenetic inactivation of SFRP genes in oral squamous cell carcinoma. Int J Oncol, 2008. 32(6): 1253–61.

    PubMed  CAS  Google Scholar 

  • Sternlicht, M.D., et al., The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell, 1999. 98(2): 137–46.

    PubMed  CAS  Google Scholar 

  • Stone, D.M., et al., The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature, 1996. 384(6605): 129–34.

    PubMed  CAS  Google Scholar 

  • Suzuki, H., et al., Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet, 2004. 36(4): 417–22.

    PubMed  CAS  Google Scholar 

  • Szabowski, A., et al., c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin. Cell, 2000. 103(5): 745–55.

    PubMed  CAS  Google Scholar 

  • Taipale, J., et al., Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature, 2000. 406(6799): 1005–9.

    PubMed  CAS  Google Scholar 

  • Taipale, J. and P. A. Beachy, The Hedgehog and Wnt signalling pathways in cancer. Nature, 2001. 411(6835): 349–54.

    PubMed  CAS  Google Scholar 

  • Tamai, K., et al., LDL-receptor-related proteins in Wnt signal transduction. Nature, 2000. 407(6803): 530–5.

    PubMed  CAS  Google Scholar 

  • Thompson, B.J., et al., Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev Cell, 2005. 9(5): 711–20.

    PubMed  CAS  Google Scholar 

  • Uematsu, K., et al., Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene, 2003. 22(46): 7218–21.

    PubMed  CAS  Google Scholar 

  • Uren, A., et al., Secreted frizzled-related protein-1 binds directly to Wingless and is a biphasic modulator of Wnt signaling. J Biol Chem, 2000. 275(6): 4374–82.

    PubMed  CAS  Google Scholar 

  • Vaccari, T. and D. Bilder, The Drosophila tumor suppressor vps25 prevents nonautonomous overproliferation by regulating notch trafficking. Dev Cell, 2005. 9(5): 687–98.

    PubMed  CAS  Google Scholar 

  • van de Wetering, M., et al., The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell, 2002. 111(2): 241–50.

    PubMed  Google Scholar 

  • van den Brink, G.R., et al., Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat Genet, 2004. 36(3): 277–82.

    PubMed  Google Scholar 

  • Van Lommel, A., et al., The pulmonary neuroendocrine system: the past decade. Arch Histol Cytol, 1999. 62(1): 1–16.

    PubMed  Google Scholar 

  • van Tuyl, M. and M. Post, From fruitflies to mammals: mechanisms of signalling via the Sonic hedgehog pathway in lung development. Respir Res, 2000. 1(1): 30–5.

    PubMed  Google Scholar 

  • Varjosalo, M. and J. Taipale, Hedgehog signaling. J Cell Sci, 2007. 120(Pt 1): 3–6.

    PubMed  CAS  Google Scholar 

  • Varnum-Finney, B., et al., Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med, 2000. 6(11): 1278–81.

    PubMed  CAS  Google Scholar 

  • Veeman, M.T., J. D. Axelrod, and R. T. Moon, A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell, 2003. 5(3): 367–77.

    PubMed  CAS  Google Scholar 

  • Vescovi, A.L., R. Galli, and B. A. Reynolds, Brain tumour stem cells. Nat Rev Cancer, 2006. 6(6): 425–36.

    PubMed  CAS  Google Scholar 

  • Virchow, R., Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre. 1858, Berlin.

    Google Scholar 

  • Voas, M.G. and I. Rebay, Signal integration during development: insights from the Drosophila eye. Dev Dyn, 2004. 229(1): 162–75.

    PubMed  CAS  Google Scholar 

  • Wang, Z., et al., Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5. Mol Cell Biol, 2005. 25(12): 5022–30.

    PubMed  CAS  Google Scholar 

  • Watkins, D.N., et al., Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature, 2003. 422(6929): 313–7.

    PubMed  CAS  Google Scholar 

  • Wechsler-Reya, R.J. and M. P. Scott, Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron, 1999. 22(1): 103–14.

    PubMed  CAS  Google Scholar 

  • Wicha, M.S., S. Liu, and G. Dontu, Cancer stem cells: an old idea—a paradigm shift. Cancer Res, 2006. 66(4): 1883–90; discussion 1895–6.

    PubMed  CAS  Google Scholar 

  • Widelitz, R., Wnt signaling through canonical and non-canonical pathways: recent progress. Growth Factors, 2005. 23(2): 111–6.

    PubMed  CAS  Google Scholar 

  • Wikenheiser, K.A., et al., Simian virus 40 large T antigen directed by transcriptional elements of the human surfactant protein C gene produces pulmonary adenocarcinomas in transgenic mice. Cancer Res, 1992. 52(19): 5342–52.

    PubMed  CAS  Google Scholar 

  • Wikenheiser-Brokamp, K.A., Rb family proteins differentially regulate distinct cell lineages during epithelial development. Development, 2004. 131(17): 4299–310.

    PubMed  CAS  Google Scholar 

  • Willert, K., et al., Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature, 2003. 423(6938): 448–52.

    PubMed  CAS  Google Scholar 

  • Williams, B.O., et al., Cooperative tumorigenic effects of germline mutations in Rb and p53. Nat Genet, 1994. 7(4): 480–4.

    PubMed  CAS  Google Scholar 

  • Wodinsky, I. and C. J. Kensler, Growth of L1210 leukemia cells. Nature, 1966. 210(5039): 962.

    PubMed  CAS  Google Scholar 

  • Xie, T. and A. C. Spradling, A niche maintaining germ line stem cells in the Drosophila ovary. Science, 2000. 290(5490): 328–30.

    PubMed  CAS  Google Scholar 

  • You, L., et al., Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene, 2004. 23(36): 6170–4.

    PubMed  CAS  Google Scholar 

  • Zhai, L., D. Chaturvedi, and S. Cumberledge, Drosophila wnt-1 undergoes a hydrophobic modification and is targeted to lipid rafts, a process that requires porcupine. J Biol Chem, 2004. 279(32): 33220–7.

    PubMed  CAS  Google Scholar 

  • Zhang, J., et al., Identification of the haematopoietic stem cell niche and control of the niche size. Nature, 2003. 425(6960): 836–41.

    PubMed  CAS  Google Scholar 

  • Zurawel, R.H., et al., Sporadic medulloblastomas contain oncogenic beta-catenin mutations. Cancer Res, 1998. 58(5): 896–9.

    PubMed  CAS  Google Scholar 

  • Zweifel, M.E., et al., Structure and stability of the ankyrin domain of the Drosophila Notch receptor. Protein Sci, 2003. 12(11): 2622–32.

    PubMed  CAS  Google Scholar 

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Acknowledgment

Supported by the Kazan Foundation and, the NIH/NCI R011R01CA093708-01A3 grant and the NIH/NCI 1R01CA132566-01 grants. We would also like to thank Dr. Geneviève Clément for helping with proof reading.

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  1. Department of Surgery, University of California San Francisco Cancer Centre, 1600 Divisadero St., Box 1724, San Francisco, CA 94143-1724, USA

    Adam Yagui-Beltrán, Biao He & David M. Jablons

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    Yagui-Beltrán, A., He, B., M. Jablons, D. (2009). Stem Cells and Lung Cancer. In: Majumder, S. (eds) Stem Cells and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89611-3_8

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