{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:18:49Z","timestamp":1790075929647,"version":"4.0.1"},"reference-count":100,"publisher":"Springer Science and Business Media LLC","issue":"7015","license":[{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2004,11]]},"DOI":"10.1038\/nature03100","type":"journal-article","created":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T01:23:39Z","timestamp":1100741019000},"page":"324-331","source":"Crossref","is-referenced-by-count":922,"title":["Tissue repair and stem cell renewal in carcinogenesis"],"prefix":"10.1038","volume":"432","author":[{"given":"Philip A.","family":"Beachy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil S.","family":"Karhadkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2004,11,17]]},"reference":[{"key":"BFnature03100_CR1","first-page":"411","volume":"46","author":"CH Park","year":"1971","unstructured":"Park, C. H., Bergsagel, D. E. & McCulloch, E. A. Mouse myeloma tumour stem cells: a primary cell culture assay. J. Natl Cancer Inst. 46, 411\u2013422 (1971).","journal-title":"J. Natl Cancer Inst."},{"key":"BFnature03100_CR2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2307\/3570892","volume":"14","author":"JE Till","year":"1961","unstructured":"Till, J. E. & McCulloch, E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res. 14, 213\u2013222 (1961).","journal-title":"Radiat. Res."},{"key":"BFnature03100_CR3","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/367645a0","volume":"367","author":"T Lapidot","year":"1994","unstructured":"Lapidot, T. et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645\u2013648 (1994).","journal-title":"Nature"},{"key":"BFnature03100_CR4","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/nm0797-730","volume":"3","author":"D Bonnet","year":"1997","unstructured":"Bonnet, D. & Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Med. 3, 730\u2013737 (1997).","journal-title":"Nature Med."},{"key":"BFnature03100_CR5","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1038\/ni1080","volume":"5","author":"KJ Hope","year":"2004","unstructured":"Hope, K. J., Jin, L. & Dick, J. E. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nature Immunol. 5, 738\u2013743 (2004).","journal-title":"Nature Immunol."},{"key":"BFnature03100_CR6","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/35077219","volume":"411","author":"J Taipale","year":"2001","unstructured":"Taipale, J. & Beachy, P. A. The Hedgehog and Wnt signalling pathways in cancer. Nature 411, 349\u2013354 (2001).","journal-title":"Nature"},{"key":"BFnature03100_CR7","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/35102167","volume":"414","author":"T Reya","year":"2001","unstructured":"Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature 414, 105\u2013111. (2001).","journal-title":"Nature"},{"key":"BFnature03100_CR8","doi-asserted-by":"publisher","first-page":"3983","DOI":"10.1073\/pnas.0530291100","volume":"100","author":"M Al-Hajj","year":"2003","unstructured":"Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA 100, 3983\u20133988 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR9","first-page":"5821","volume":"63","author":"SK Singh","year":"2003","unstructured":"Singh, S. K. et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821\u20135828 (2003).","journal-title":"Cancer Res."},{"key":"BFnature03100_CR10","doi-asserted-by":"publisher","first-page":"15178","DOI":"10.1073\/pnas.2036535100","volume":"100","author":"HD Hemmati","year":"2003","unstructured":"Hemmati, H. D. et al. Cancerous stem cells can arise from pediatric brain tumors. Proc. Natl Acad. Sci. USA 100, 15178\u201315183 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR11","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1073\/pnas.0307618100","volume":"101","author":"T Kondo","year":"2004","unstructured":"Kondo, T., Setoguchi, T. & Taga, T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc. Natl Acad. Sci. USA 101, 781\u2013786 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"issue":"suppl. 1","key":"BFnature03100_CR12","doi-asserted-by":"publisher","first-page":"11842","DOI":"10.1073\/pnas.2034201100","volume":"100","author":"E Passegue","year":"2003","unstructured":"Passegue, E., Jamieson, C. H., Ailles, L. E. & Weissman, I. L. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc. Natl Acad. Sci. USA 100 (suppl. 1), 11842\u201311849 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR13","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1126\/science.1097676","volume":"304","author":"C Brawley","year":"2004","unstructured":"Brawley, C. & Matunis, E. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo. Science 304, 1331\u20131334 (2004).","journal-title":"Science"},{"key":"BFnature03100_CR14","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/nature02436","volume":"428","author":"T Kai","year":"2004","unstructured":"Kai, T. & Spradling, A. Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries. Nature 428, 564\u2013569 (2004).","journal-title":"Nature"},{"key":"BFnature03100_CR15","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1101\/gad.938601","volume":"15","author":"PW Ingham","year":"2001","unstructured":"Ingham, P. W. & McMahon, A. P. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 15, 3059\u20133087 (2001).","journal-title":"Genes Dev."},{"key":"BFnature03100_CR16","unstructured":"Muenke, M. & Beachy, P. A. in The Metabolic and Molecular Bases of Inherited Disease (eds Scriver, C. et al.) 6203\u20136230 (McGraw-Hill, New York, 2001)."},{"key":"BFnature03100_CR17","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1146\/annurev.cellbio.20.010403.113126","volume":"20","author":"CY Logan","year":"2004","unstructured":"Logan, C. Y. & Nusse, R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell. Dev. Biol. 20, 781\u2013810 (2004).","journal-title":"Annu. Rev. Cell. Dev. Biol"},{"key":"BFnature03100_CR18","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/35069099","volume":"410","author":"Y Zhang","year":"2001","unstructured":"Zhang, Y. & Kalderon, D. Hedgehog acts as a somatic stem cell factor in the Drosophila ovary. Nature 410, 599\u2013604 (2001).","journal-title":"Nature"},{"key":"BFnature03100_CR19","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/S0896-6273(03)00593-2","volume":"40","author":"R Machold","year":"2003","unstructured":"Machold, R. et al. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron 40, 189\u2013190 (2003).","journal-title":"Neuron"},{"key":"BFnature03100_CR20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/nn983","volume":"6","author":"K Lai","year":"2003","unstructured":"Lai, K., Kaspar, B. K., Gage, F. H. & Schaffer, D. V. Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nature Neurosci. 6, 21\u201327 (2003).","journal-title":"Nature Neurosci."},{"key":"BFnature03100_CR21","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1101\/gad.267103","volume":"17","author":"D Pinto","year":"2003","unstructured":"Pinto, D., Gregorieff, A., Begthel, H. & Clevers, H. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev. 17, 1709\u20131713 (2003).","journal-title":"Genes Dev."},{"key":"BFnature03100_CR22","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/nature01593","volume":"423","author":"T Reya","year":"2003","unstructured":"Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409\u2013414 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR23","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/S0092-8674(03)00437-9","volume":"113","author":"A Polesskaya","year":"2003","unstructured":"Polesskaya, A., Seale, P. & Rudnicki, M. A. Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration. Cell 113, 841\u2013852 (2003).","journal-title":"Cell"},{"key":"BFnature03100_CR24","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/nrc1096","volume":"3","author":"DM Owens","year":"2003","unstructured":"Owens, D. M. & Watt, F. M. Contribution of stem cells and differentiated cells to epidermal tumours. Nature Rev. Cancer 3, 444\u2013451 (2003).","journal-title":"Nature Rev. Cancer"},{"key":"BFnature03100_CR25","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/nrc1095","volume":"3","author":"J Perez-Losada","year":"2003","unstructured":"Perez-Losada, J. & Balmain, A. Stem-cell hierarchy in skin cancer. Nature Rev. Cancer 3, 434\u2013443 (2003).","journal-title":"Nature Rev. Cancer"},{"key":"BFnature03100_CR26","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/1270","volume":"19","author":"V Korinek","year":"1998","unstructured":"Korinek, V. et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nature Genet. 19, 379\u2013383 (1998).","journal-title":"Nature Genet."},{"key":"BFnature03100_CR27","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/84282","volume":"2","author":"G Bhardwaj","year":"2001","unstructured":"Bhardwaj, G. et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nature Immunol. 2, 172\u2013180 (2001).","journal-title":"Nature Immunol."},{"key":"BFnature03100_CR28","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1242\/dev.127.12.2763","volume":"127","author":"M Ramalho-Santos","year":"2000","unstructured":"Ramalho-Santos, M., Melton, D. A. & McMahon, A. P. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127, 2763\u20132772 (2000).","journal-title":"Development"},{"key":"BFnature03100_CR29","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/nature02962","volume":"431","author":"SS Karhadkar","year":"2004","unstructured":"Karhadkar, S. S. et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431, 707\u2013712 (2004).","journal-title":"Nature"},{"key":"BFnature03100_CR30","unstructured":"Cancer facts and figures. Am. Cancer Soc. \u3008 http:\/\/www.cancer.org \u3009 (2003)."},{"key":"BFnature03100_CR31","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1146\/annurev.neuro.24.1.385","volume":"24","author":"R Wechsler-Reya","year":"2001","unstructured":"Wechsler-Reya, R. & Scott, M. P. The developmental biology of brain tumors. Annu. Rev. Neurosci. 24, 385\u2013428 (2001).","journal-title":"Annu. Rev. Neurosci."},{"key":"BFnature03100_CR32","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1126\/science.1098020","volume":"304","author":"L Lum","year":"2004","unstructured":"Lum, L. & Beachy, P. A. The Hedgehog response network: sensors, switches, and routers. Science 304, 1755\u20131759 (2004).","journal-title":"Science"},{"key":"BFnature03100_CR33","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1146\/annurev.biochem.73.011303.073933","volume":"73","author":"RK Mann","year":"2004","unstructured":"Mann, R. K. & Beachy, P. A. Novel lipid modification of secreted protein signals. Annu. Rev. Biochem. 73, 891\u2013923 (2004).","journal-title":"Annu. Rev. Biochem."},{"key":"BFnature03100_CR34","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1242\/dev.01122","volume":"131","author":"OV Bulgakov","year":"2004","unstructured":"Bulgakov, O. V., Eggenschwiler, J. T., Hong, D. H., Anderson, K. V. & Li, T. FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues. Development 131, 2149\u20132159 (2004).","journal-title":"Development"},{"key":"BFnature03100_CR35","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/35084089","volume":"412","author":"JT Eggenschwiler","year":"2001","unstructured":"Eggenschwiler, J. T., Espinoza, E. & Anderson, K. V. Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature 412, 194\u2013198 (2001).","journal-title":"Nature"},{"key":"BFnature03100_CR36","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1038\/39918","volume":"389","author":"N Dahmane","year":"1997","unstructured":"Dahmane, N., Lee, J., Robins, P., Heller, P. & Altaba, R. I. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature 389, 876\u2013881 (1997).","journal-title":"Nature"},{"key":"BFnature03100_CR37","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1126\/science.1073733","volume":"297","author":"DM Berman","year":"2002","unstructured":"Berman, D. M. et al. Medulloblastoma growth inhibition by hedgehog pathway blockade. Science 297, 1559\u20131561 (2002).","journal-title":"Science"},{"key":"BFnature03100_CR38","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/35023008","volume":"406","author":"J Taipale","year":"2000","unstructured":"Taipale, J. et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature 406, 1005\u20131009 (2000).","journal-title":"Nature"},{"key":"BFnature03100_CR39","doi-asserted-by":"publisher","first-page":"2743","DOI":"10.1101\/gad.1025302","volume":"16","author":"JK Chen","year":"2002","unstructured":"Chen, J. K., Taipale, J., Cooper, M. K. & Beachy, P. A. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16, 2743\u20132748 (2002).","journal-title":"Genes Dev."},{"key":"BFnature03100_CR40","doi-asserted-by":"publisher","first-page":"14071","DOI":"10.1073\/pnas.182542899","volume":"99","author":"JK Chen","year":"2002","unstructured":"Chen, J. K., Taipale, J., Young, K. E., Maiti, T. & Beachy, P. A. Small molecule modulation of Smoothened activity. Proc. Natl Acad. Sci. USA 99, 14071\u20131406 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR41","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nature01493","volume":"422","author":"DN Watkins","year":"2003","unstructured":"Watkins, D. N. et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 422, 313\u2013317 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR42","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1038\/nature01972","volume":"425","author":"DM Berman","year":"2003","unstructured":"Berman, D. M. et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425, 846\u2013851 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR43","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/nature02009","volume":"425","author":"SP Thayer","year":"2003","unstructured":"Thayer, S. P. et al. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425, 851\u2013856 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR44","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0092-8674(82)90409-3","volume":"31","author":"R Nusse","year":"1982","unstructured":"Nusse, R. & Varmus, H. E. Many tumors induced by the mouse mammary tumour virus contain a provirus integrated in the same region of the host genome. Cell 31, 99\u2013109 (1982).","journal-title":"Cell"},{"key":"BFnature03100_CR45","first-page":"1","volume":"1653","author":"RH Giles","year":"2003","unstructured":"Giles, R. H., van Es, J. H. & Clevers, H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta. 1653, 1\u201324 (2003).","journal-title":"Biochim. Biophys. Acta."},{"key":"BFnature03100_CR46","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1242\/dev.01117","volume":"131","author":"X He","year":"2004","unstructured":"He, X., Semenov, M., Tamai, K. & Zeng, X. LDL receptor-related proteins 5 and 6 in Wnt\/beta-catenin signaling: arrows point the way. Development 131, 1663\u20131677 (2004).","journal-title":"Development"},{"key":"BFnature03100_CR47","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/ng1330","volume":"36","author":"H Suzuki","year":"2004","unstructured":"Suzuki, H. et al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nature Genet. 36, 417\u2013422 (2004).","journal-title":"Nature Genet."},{"key":"BFnature03100_CR48","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S1535-6108(03)00334-9","volume":"5","author":"M Lepourcelet","year":"2004","unstructured":"Lepourcelet, M. et al. Small-molecule antagonists of the oncogenic Tcf\/beta-catenin protein complex. Cancer Cell 5, 91\u2013102 (2004).","journal-title":"Cancer Cell"},{"key":"BFnature03100_CR49","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/35025063","volume":"407","author":"B Hobmayer","year":"2000","unstructured":"Hobmayer, B. et al. WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra. Nature 407, 186\u2013189 (2000).","journal-title":"Nature"},{"key":"BFnature03100_CR50","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.ydbio.2003.12.005","volume":"267","author":"PA Tsonis","year":"2004","unstructured":"Tsonis, P. A. et al. A novel role of the hedgehog pathway in lens regeneration. Dev. Biol. 267, 450\u2013461 (2004).","journal-title":"Dev. Biol."},{"key":"BFnature03100_CR51","doi-asserted-by":"publisher","first-page":"9159","DOI":"10.1073\/pnas.94.17.9159","volume":"94","author":"Y Imokawa","year":"1997","unstructured":"Imokawa, Y. & Yoshizato, K. Expression of Sonic hedgehog gene in regenerating newt limb blastemas recapitulates that in developing limb buds. Proc. Natl Acad. Sci. USA 94, 9159\u20139164 (1997).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR52","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/jez.10110","volume":"293","author":"S Roy","year":"2002","unstructured":"Roy, S. & Gardiner, D. M. Cyclopamine induces digit loss in regenerating axolotl limbs. J. Exp. Zool. 293, 186\u2013190 (2002).","journal-title":"J. Exp. Zool."},{"key":"BFnature03100_CR53","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1242\/dev.125.21.4175","volume":"125","author":"L Laforest","year":"1998","unstructured":"Laforest, L. et al. Involvement of the sonic hedgehog, patched 1 and bmp2 genes in patterning of the zebrafish dermal fin rays. Development 125, 4175\u20134184 (1998).","journal-title":"Development"},{"key":"BFnature03100_CR54","doi-asserted-by":"publisher","first-page":"8713","DOI":"10.1073\/pnas.122571799","volume":"99","author":"E Quint","year":"2002","unstructured":"Quint, E. et al. Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine. Proc. Natl Acad .Sci. USA 99, 8713\u20138718 (2002).","journal-title":"Proc. Natl Acad .Sci. USA"},{"key":"BFnature03100_CR55","doi-asserted-by":"publisher","first-page":"4158","DOI":"10.1073\/pnas.0400699101","volume":"101","author":"BY Liu","year":"2004","unstructured":"Liu, B. Y., McDermott, S. P., Khwaja, S. S. & Alexander, C. M. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc. Natl Acad. Sci. USA 101, 4158\u20134163 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR56","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1136\/gut.49.4.565","volume":"49","author":"NA Shackel","year":"2001","unstructured":"Shackel, N. A., McGuinness, P. H., Abbott, C. A., Gorrell, M. D. & McCaughan, G. W. Identification of novel molecules and pathogenic pathways in primary biliary cirrhosis: cDNA array analysis of intrahepatic differential gene expression. Gut 49, 565\u2013576 (2001).","journal-title":"Gut"},{"key":"BFnature03100_CR57","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1053\/jhep.2001.23786","volume":"33","author":"SP Monga","year":"2001","unstructured":"Monga, S. P., Pediaditakis, P., Mule, K., Stolz, D. B. & Michalopoulos, G. K. Changes in WNT\/beta-catenin pathway during regulated growth in rat liver regeneration. Hepatology 33, 1098\u20131109 (2001).","journal-title":"Hepatology"},{"key":"BFnature03100_CR58","doi-asserted-by":"publisher","first-page":"F653","DOI":"10.1152\/ajprenal.00343.2002","volume":"284","author":"K Surendran","year":"2003","unstructured":"Surendran, K. & Simon, T. C. CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury. Am. J. Physiol. Renal Physiol. 284, F653\u2013F662 (2003).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"BFnature03100_CR59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00418-003-0501-z","volume":"119","author":"T Miyaji","year":"2003","unstructured":"Miyaji, T. et al. Expression and distribution of transcripts for sonic hedgehog in the early phase of fracture repair. Histochem. Cell Biol. 119, 233\u2013237 (2003).","journal-title":"Histochem. Cell Biol."},{"key":"BFnature03100_CR60","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/nature01322","volume":"420","author":"LM Coussens","year":"2002","unstructured":"Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860\u2013867 (2002).","journal-title":"Nature"},{"key":"BFnature03100_CR61","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1056\/NEJM198612253152606","volume":"315","author":"HF Dvorak","year":"1986","unstructured":"Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumour stroma generation and wound healing. N. Engl. J. Med. 315, 1650\u20131659 (1986).","journal-title":"N. Engl. J. Med."},{"key":"BFnature03100_CR62","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1023\/A:1011290704728","volume":"12","author":"AH Wu","year":"2001","unstructured":"Wu, A. H., Wan, P. & Bernstein, L. A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States). Cancer Causes Control 12, 721\u2013732 (2001).","journal-title":"Cancer Causes Control"},{"key":"BFnature03100_CR63","first-page":"2863","volume":"39","author":"CS Lieber","year":"1979","unstructured":"Lieber, C. S., Seitz, H. K., Garro, A. J. & Worner, T. M. Alcohol-related diseases and carcinogenesis. Cancer Res. 39, 2863\u20132886 (1979).","journal-title":"Cancer Res."},{"key":"BFnature03100_CR64","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1023\/A:1018417623867","volume":"8","author":"A Blair","year":"1997","unstructured":"Blair, A. & Kazerouni, N. Reactive chemicals and cancer. Cancer Causes Control 8, 473\u2013490 (1997).","journal-title":"Cancer Causes Control"},{"key":"BFnature03100_CR65","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1056\/NEJMoa001999","volume":"345","author":"N Uemura","year":"2001","unstructured":"Uemura, N. et al. Helicobacter pylori infection and the development of gastric cancer. N. Engl. J. Med. 345, 784\u2013789 (2001).","journal-title":"N. Engl. J. Med."},{"key":"BFnature03100_CR66","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1056\/NEJM199011013231802","volume":"323","author":"A Ekbom","year":"1990","unstructured":"Ekbom, A., Helmick, C., Zack, M. & Adami, H. O. Ulcerative colitis and colorectal cancer. A population-based study. N. Engl. J. Med. 323, 1228\u20131233 (1990).","journal-title":"N. Engl. J. Med."},{"key":"BFnature03100_CR67","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/j.1572-0241.2004.04067.x","volume":"99","author":"K Burak","year":"2004","unstructured":"Burak, K. et al. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis. Am. J. Gastroenterol. 99, 523\u2013526 (2004).","journal-title":"Am. J. Gastroenterol."},{"key":"BFnature03100_CR68","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature01572","volume":"423","author":"J Lessard","year":"2003","unstructured":"Lessard, J. & Sauvageau, G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423, 255\u2013260 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR69","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nature01587","volume":"423","author":"IK Park","year":"2003","unstructured":"Park, I. K. et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302\u2013305 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR70","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/nature02060","volume":"425","author":"AV Molofsky","year":"2003","unstructured":"Molofsky, A. V. et al. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425, 962\u2013967 (2003).","journal-title":"Nature"},{"key":"BFnature03100_CR71","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature02385","volume":"428","author":"C Leung","year":"2004","unstructured":"Leung, C. et al. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428, 337\u2013341 (2004).","journal-title":"Nature"},{"key":"BFnature03100_CR72","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1006\/bbrc.1999.1197","volume":"262","author":"H Ito","year":"1999","unstructured":"Ito, H. et al. Hedgehog signaling molecules in bone marrow cells at the initial stage of fracture repair. Biochem. Biophys. Res. Commun. 262, 443\u2013451 (1999).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnature03100_CR73","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/(SICI)1097-0215(19990812)82:4<504::AID-IJC6>3.0.CO;2-6","volume":"82","author":"TJ Hugh","year":"1999","unstructured":"Hugh, T. J. et al. beta-catenin expression in primary and metastatic colorectal carcinoma. Int. J. Cancer 82, 504\u2013511 (1999).","journal-title":"Int. J. Cancer"},{"key":"BFnature03100_CR74","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/35000025","volume":"2","author":"A Cano","year":"2000","unstructured":"Cano, A. et al. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biol. 2, 76\u201383 (2000).","journal-title":"Nature Cell Biol."},{"key":"BFnature03100_CR75","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.cell.2004.06.006","volume":"117","author":"J Yang","year":"2004","unstructured":"Yang, J. et al. Twist a master regulator of morphogenesis, plays an essential role in tumour metastasis. Cell 117, 927\u2013939 (2004).","journal-title":"Cell"},{"key":"BFnature03100_CR76","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1083\/jcb.200308162","volume":"163","author":"M Conacci-Sorrell","year":"2003","unstructured":"Conacci-Sorrell, M. et al. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J. Cell Biol. 163, 847\u2013857 (2003).","journal-title":"J. Cell Biol"},{"key":"BFnature03100_CR77","doi-asserted-by":"publisher","first-page":"10356","DOI":"10.1073\/pnas.171610498","volume":"98","author":"T Brabletz","year":"2001","unstructured":"Brabletz, T. et al. Variable beta-catenin expression in colorectal cancers indicates tumour progression driven by the tumour environment. Proc. Natl Acad. Sci. USA 98, 10356\u201310361 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR78","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1042\/cs0930097","volume":"93","author":"AJ Wilson","year":"1997","unstructured":"Wilson, A. J. & Gibson, P. R. Epithelial migration in the colon: filling in the gaps. Clin. Sci. (Lond) 93, 97\u2013108 (1997).","journal-title":"Clin. Sci. (Lond)"},{"key":"BFnature03100_CR79","doi-asserted-by":"publisher","first-page":"4633","DOI":"10.1073\/pnas.0830856100","volume":"100","author":"T Kai","year":"2003","unstructured":"Kai, T. & Spradling, A. An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells. Proc. Natl Acad. Sci. USA 100, 4633\u20134638 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR80","doi-asserted-by":"publisher","first-page":"196","DOI":"10.4161\/cc.2.3.378","volume":"2","author":"DN Watkins","year":"2003","unstructured":"Watkins, D. N., Berman, D. M. & Baylin, S. B. Hedgehog signaling: progenitor phenotype in small-cell lung cancer. Cell Cycle 2, 196\u2013198 (2003).","journal-title":"Cell Cycle"},{"key":"BFnature03100_CR81","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ccr.2004.08.019","volume":"6","author":"JT Romer","year":"2004","unstructured":"Romer, J. T. et al. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+\/\u2212p53\u2212\/\u2212mice. Cancer Cell 6, 229\u2013240 (2004).","journal-title":"Cancer Cell"},{"key":"BFnature03100_CR82","first-page":"96","volume":"14","author":"S Tas","year":"2004","unstructured":"Tas, S. & Avci, O. Induction of the differentiation and apoptosis of tumour cells in vivo with efficiency and selectivity. Eur. J. Dermatol. 14, 96\u2013102 (2004).","journal-title":"Eur. J. Dermatol."},{"key":"BFnature03100_CR83","doi-asserted-by":"publisher","first-page":"4616","DOI":"10.1073\/pnas.0732813100","volume":"100","author":"JA Williams","year":"2003","unstructured":"Williams, J. A. et al. Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions. Proc. Natl Acad. Sci. USA 100, 4616\u20134621 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR84","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1182\/blood.V89.10.3624","volume":"89","author":"TW Austin","year":"1997","unstructured":"Austin, T. W., Solar, G. P., Ziegler, F. C., Liem, L. & Matthews, W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood 89, 3624\u20133635 (1997).","journal-title":"Blood"},{"key":"BFnature03100_CR85","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1182\/blood.V92.9.3189","volume":"92","author":"DJ van den Berg","year":"1998","unstructured":"van den Berg, D. J., Sharma, A. K., Bruno, E. & Hoffman, R. Role of members of the Wnt gene family in human hematopoiesis. Blood 92, 3189\u20133202 (1998).","journal-title":"Blood"},{"key":"BFnature03100_CR86","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/ng916","volume":"31","author":"MD Taylor","year":"2002","unstructured":"Taylor, M. D. et al. Mutations in SUFU predispose to medulloblastoma. Nature Genet. 31, 306\u2013311 (2002).","journal-title":"Nature Genet."},{"key":"BFnature03100_CR87","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1126\/science.3563490","volume":"236","author":"KW Kinzler","year":"1987","unstructured":"Kinzler, K. W. et al. Identification of an amplified, highly expressed gene in a human glioma. Science 236, 70\u201373 (1987).","journal-title":"Science"},{"key":"BFnature03100_CR88","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1242\/dev.128.24.5201","volume":"128","author":"N Dahmane","year":"2001","unstructured":"Dahmane, N. et al. The Sonic Hedgehog-Gli pathway regulates dorsal brain growth and tumorigenesis. Development 128, 5201\u20135212 (2001).","journal-title":"Development"},{"key":"BFnature03100_CR89","doi-asserted-by":"publisher","first-page":"3961","DOI":"10.1210\/en.2004-0079","volume":"145","author":"L Fan","year":"2004","unstructured":"Fan, L. et al. Hedgehog signaling promotes prostate xenograft tumour growth. Endocrinology 145, 3961\u20133970 (2004).","journal-title":"Endocrinology"},{"key":"BFnature03100_CR90","doi-asserted-by":"publisher","first-page":"12561","DOI":"10.1073\/pnas.0404956101","volume":"101","author":"P Sanchez","year":"2004","unstructured":"Sanchez, P. et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc. Natl Acad. Sci. USA 101, 12561\u201312566 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR91","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1158\/0008-5472.CAN-03-2031","volume":"64","author":"S Hamed","year":"2004","unstructured":"Hamed, S. et al. Accelerated induction of bladder cancer in patched heterozygous mutant mice. Cancer Res. 64, 1938\u20131942 (2004).","journal-title":"Cancer Res."},{"key":"BFnature03100_CR92","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.bbrc.2003.12.097","volume":"314","author":"H Nishimaki","year":"2004","unstructured":"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. 314, 313\u2013320 (2004).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnature03100_CR93","doi-asserted-by":"publisher","first-page":"6122","DOI":"10.1073\/pnas.0305855101","volume":"101","author":"PW Derksen","year":"2004","unstructured":"Derksen, P. W. et al. Illegitimate WNT signaling promotes proliferation of multiple myeloma cells. Proc. Natl Acad. Sci. USA 101, 6122\u20136127 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature03100_CR94","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.1158\/0008-5472.CAN-03-1952","volume":"64","author":"BH Hoang","year":"2004","unstructured":"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. 64, 2734\u20132739 (2004).","journal-title":"Cancer Res."},{"key":"BFnature03100_CR95","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/ijc.11677","volume":"109","author":"BH Hoang","year":"2004","unstructured":"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 109, 106\u2013111 (2004).","journal-title":"Int. J. Cancer"},{"key":"BFnature03100_CR96","doi-asserted-by":"publisher","first-page":"6170","DOI":"10.1038\/sj.onc.1207844","volume":"23","author":"L You","year":"2004","unstructured":"You, L. et al. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells. Oncogene 23, 6170\u20136174 (2004).","journal-title":"Oncogene"},{"key":"BFnature03100_CR97","doi-asserted-by":"publisher","first-page":"6672","DOI":"10.1038\/sj.onc.1207881","volume":"23","author":"AY Lee","year":"2004","unstructured":"Lee, A. Y. et al. Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma. Oncogene 23, 6672\u20136676 (2004).","journal-title":"Oncogene"},{"key":"BFnature03100_CR98","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1161\/01.CIR.0000080338.60981.FA","volume":"108","author":"R Pola","year":"2003","unstructured":"Pola, R. et al. Postnatal recapitulation of embryonic hedgehog pathway in response to skeletal muscle ischemia. Circulation 108, 479\u2013485 (2003).","journal-title":"Circulation"},{"key":"BFnature03100_CR99","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1523\/JNEUROSCI.2980-03.2004","volume":"24","author":"A Moshiri","year":"2004","unstructured":"Moshiri, A. & Reh, T. A. Persistent progenitors at the retinal margin of ptc+\/\u2212 mice. J. Neurosci. 24, 229\u2013237 (2004).","journal-title":"J. Neurosci."},{"key":"BFnature03100_CR100","doi-asserted-by":"publisher","first-page":"7923","DOI":"10.1523\/JNEUROSCI.1784-04.2004","volume":"24","author":"C Akazawa","year":"2004","unstructured":"Akazawa, C. et al. The upregulated expression of sonic hedgehog in motor neurons after rat facial nerve axotomy. J. Neurosci. 24, 7923\u20137930 (2004).","journal-title":"J. Neurosci."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature03100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature03100","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature03100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:28:35Z","timestamp":1684420115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature03100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,11]]},"references-count":100,"journal-issue":{"issue":"7015","published-print":{"date-parts":[[2004,11]]}},"alternative-id":["BFnature03100"],"URL":"https:\/\/doi.org\/10.1038\/nature03100","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1023164.264847","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,11]]}}}