参考文献
1.Rao T P，et al.An updated overview on Wnt signaling pathways：a prelude for more.Circ Res，2010，106（12）：1798-1806.
2.Merlos-Suarez A，et al.The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.Cell Stem Cell，2011，8（5）：511-524.
3.Brown AM.Wnt signaling in breast cancer：have we come full circle? Breast Cancer Res，2001，3（6）：351-355.
4.Barker N Catenins.Wnt signaling and cancer.Bioessays，2000，11：961-965.
5.Peifer M，et al.Wnt signaling in oncogenesis and embryogenesis-a look outside the nucleus.Science，2000，287（5458）：1606-1609.
6.He TC，et al.Identification of c-MYC as a target of the APC pathway.Science，1998，281（5382）：1509-1512.
7.Xin HW，et al.Wnt and the cancer niche：paracrine interactions with gastrointestinal cancer cells undergoing asymmetric cell division.J Cancer，2013，4（6）：447-457.
8.Yeung J，et al.beta-Catenin mediates the establishment and drug resistance of MLL leukemic stem cells.Cancer Cell，2010，18（6）：606-618.
9.Jamieson CH，et al.Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML.N Engl J Med，2004，351（7）：657-667.
10.Kruger JA，et al.Characterization of stem cell-like cancer cells in immune-competent mice.Blood，2006，108（12）：3906-3912.
11.Barker N，et al.Crypt stem cells as the cells-of-origin of intestinal cancer.Nature，2009，457（7229）：608-611.
12.Barker N，et al.Mining the Wnt pathway for cancer therapeutics.Nat Rev Drug Discov，2006，5（12）：997-1014.
13.Lee HS，et al.Clinical significance of serum and tissue Dickkopf-1 levels in patients with gastric cancer.Clin Chim Acta，2012，413（21-22）：1753-1760.
14.Martinico SC，et al.Assessment of endostatin gene therapy for familial adenomatous polyposis-related desmoid tumors.Cancer Res，2006，66（16）：8233-8240.
15.Chien AJ，et al.A Wnt survival guide：from flies to human disease.J Invest Dermatol，2009，129（7）：1614-1627.
16.Mikheev AM，et al.Dickkopf-1 mediated tumor suppression in human breast carcinoma cells.Breast Cancer Res Treat，2008，112（2）：263-273.
17.Chen G，et al.Stem cell-targeted therapy-a new strategy for cancer treatment.Zhonghua Zhong Liu Za Zhi，2008，11：801-803.
18.Katoh M.WNT signaling pathway and stem cell signaling network.Clin Cancer Res，2007，14：4042-4045.
19.Green DW，et al.Beta-catenin antisense treatment decreases beta-catenin expression and tumor growth rate in colon carcinoma xenografts.J Surg Res，2001，101（1）：16-20.
20.Veeramachaneni NK，et al.Down-regulation of beta catenin inhibits the growth of esophageal carcinoma cells.J Thorac Cardiovasc Surg，2004，127（1）：92-98.
21.Cong F，et al.A protein knockdown strategy to study the function of beta-catenin in tumorigenesis.BMC Mol Biol，2003，4：10.
22.Zeng G，et al.siRNA-mediated beta-catenin knockdown in human hepatoma cells results in decreased growth and survival.Neoplasia，2007，9（11）：951-959.
23.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）：241-250.
24.Emami KH，et al.A small molecule inhibitor of beta-catenin/CREB-binding protein transcription ［corrected］.Proc Natl Acad Sci U S A，2004，101（34）：12682-12687.
25.Sato C，et al.An overview of notch signaling in adult tissue renewal and maintenance.Curr Alzheimer Res，2012，9（2）：227-240.
26.Artavanis-Tsakonas S，et al.Notch signaling：cell fate control and signal integration in development.Science，1999，284（5415）：770-776.
27.Holland LZ，et al.Characterization and developmental expression of the amphioxus homolog of Notch（AmphiNotch）：evolutionary conservation of multiple expression domains in amphioxus and vertebrates.Dev Biol，2001，232（2）：493-507.
28.Jubb AM，et al.Expression of vascular Notch ligands Delta-like 4 and Jagged-1 in glioblastoma.Histopathology，2012，60（5）：740-747.
29.Amsen D，et al.Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells.Cell，2004，117（4）：515-526.
30.Miele L.Notch signaling.Clin Cancer Res，2006，12：1074-1079.
31.Baron M.An overview of the Notch signalling pathway.Semin Cell Dev Biol，2003，14：113-119.
32.Joseph NM，et al.Toward an understanding of the physiological function of Mammalian stem cells.Dev Cell，2005，9（2）：173-183.
33.Ohlstein B，et al.The adult Drosophila posterior midgut is maintained by pluripotent stem cells.Nature，2006，439（7075）：470-474.
34.Ohlstein B，et al.The stem cell niche：theme and variations.Curr Opin Cell Biol，2004，16（6）：693-699.
35.Wilson A，et al.Multiple functions of Notch signaling in self-renewing organs and cancer.FEBS Lett，2006，580（12）：2860-2868.
36.Fre S，et al.Notch signals control the fate of immature progenitor cells in the intestine.Nature，2005，435（7044）：964-948.
37.Ohlstein B，et al.Multipotent Drosophila intestinal stem cells specify daughter cell fates by differential notch signaling.Science，2007，315（5814）：988-992.
38.Ellisen LW，et al.TAN-1，the human homolog of the Drosophila notch gene，is broken by chromosomal translocations in T lymphoblastic neoplasms.Cell，1991，66（4）：649-661.
39.Weng AP，et al.Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia.science，2004，306（5694）：269-271.
40.Nakayama K，et al.Amplicon profiles in ovarian serous carcinomas.Int J Cancer，2007，120（12）：2613-2617.
41.Pece S，et al.Loss of negative regulation by Numb over Notch is relevant to human breast carcinogenesis.J Cell Biol，2004，167（2）：215-221.
42.Yoon K，et al.Notch signaling in the mammalian central nervous system：insights from mouse mutants.Nat Neurosci，2005，8（6）：709-715.
43.Dontu G，et al.Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells.Breast Cancer Res，2004，6（6）：R605-615.
44.Hitoshi S，et al.Notch pathway molecules are essential for the maintenance，but not the generation，of mammalian neural stem cells.Genes Dev，2002，16（7）：846-858.
45.Pierfelice TJ，et al.Notch，neural stem cells，and brain tumors.Cold Spring Harb Symp Quant Biol，2008，73：367-375.
46.Stockhausen MT，et al.The functional role of Notch signaling in human gliomas.Neuro Oncol，2010，12（2）：199-211.
47.Ables JL，et al.Not（ch）just development：Notch signalling in the adult brain.Nat Rev Neurosci，2011，12（5）：269-283.
48.Main H，et al.Notch signaling maintains neural rosette polarity.PLoS One，2013，8（5）：e62959.
49.Mellodew K，et al.Nestin expression is lost in a neural stem cell line through a mechanism involving the proteasome and Notch signalling.Brain Res Dev Brain Res，2004，151（1-2）：13-23.
50.Zhang XP，et al.Notch activation promotes cell proliferation and the formation of neural stem cell-like colonies in human glioma cells.Mol Cell Biochem，2008，307（1-2）：101-108.
51.Fan X，et al.Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors.Cancer Res，2006，66（15）：7445-7452.
52.Liu S，et al.Mammary stem cells，self-renewal pathways，and carcinogenesis.Breast Cancer Res，2005，7（3）：86-95.
53.Dickson BC，et al.High-level JAG1 mRNA and protein predict poor outcome in breast cancer.Mod Pathol，2007，20（6）：685-693.
54.Reedijk M，et al.High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival.Cancer Res，2005，65（18）：8530-8537.
55.Magnifico A，et al.Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab.Clin Cancer Res，2009，15（6）：2010-2021.
56.Farnie G，et al.Mammary stem cells and breast cancer—role of Notch signalling.Stem Cell Rev，2007，3（2）：169-175.
57.Phillips TM，et al.Effects of recombinant erythropoietin on breast cancer-initiating cells.Neoplasia，2007，9（12）：1122-1129.
58.Sansone P，et al.p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres.Stem Cells，2007，25（3）：807-815.
59.Sansone P，et al.IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland.J Clin Invest，2007，117（12）：3988-4002.
60.Gal H，et al.Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells.Leukemia，2006，20（12）：2147-2154.
61.van Es JH，et al.Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells.Nature，2005，435（7044）：959-963.
62.Schroder N，et al.Expression of Notch pathway components in fetal and adult mouse small intestine.Gene Expr Patterns，2002，2（3-4）：247-250.
63.Sander GR，et al.Expression of notch receptors and ligands in the adult gut.J Histochem Cytochem，2004，52（4）：509-516.
64.Kosinski C，et al.Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors.Proc Natl Acad Sci U S A，2007，104（39）：15418-15423.
65.Sureban SM，et al.Knockdown of RNA binding protein musashi-1 leads to tumor regression in vivo.Gastroenterology，2008，134（5）：1448-1458.
66.Won HY，et al.Loss of Mel-18 enhances breast cancer stem cell activity and tumorigenicity through activating Notch signaling mediated by the Wnt/TCF pathway.FASEB J，2012，26（12）：5002-5013.
67.Tzoneva G，et al.Recent advances on NOTCH signaling in T-ALL.Curr Top Microbiol Immunol，2012，360：163-182.
68.Purow B.Notch inhibition as a promising new approach to cancer therapy.Adv Exp Med Biol，2012，727：305-319.
69.Al-Hussaini H，et al.Notch signaling pathway as a therapeutic target in breast cancer.Mol Cancer Ther，2011，10（1）：9-15.
70.Krop I，et al.PhaseⅠpharmacologic and pharmacodynamic study of the gamma secretase（Notch）inhibitor MK-0752 in adult patients with advanced solid tumors.J Clin Oncol，2012，30（19）：2307-2313.
71.Strosberg JR，et al.A phase Ⅱ study of RO4929097 in metastatic colorectal cancer.Eur J Cancer，2012，48（7）：997-1003.
72.Kolb EA，et al.Initial testing（stage 1）by the pediatric preclinical testing program of RO4929097，a gammasecretase inhibitor targeting notch signaling.Pediatr Blood Cancer，2012，58（5）：815-818.
73.Rizzo P，et al.Rational targeting of Notch signaling in cancer.Oncogene，2008，27（38）：5124-5131.
74.Duarte A，et al.Dosage-sensitive requirement for mouse Dll4 in artery development.Genes Dev，2004，18（20）：2474-2478.
75.Suchting S，et al.The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching.Proc Natl Acad Sci U S A，2007，104（9）：3225-3230.
76.Ridgway J，et al.Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis.Nature，2006，444（7122）：1083-1087.
77.Yan M，et al.Chronic DLL4 blockade induces vascular neoplasms.Nature，2010，463（7282）：6-7.
78.van den Brink GR，et al.Sonic hedgehog regulates gastric gland morphogenesis in man and mouse.Gastroenterology，2001，121（2）：317-328.
79.Kai T，et al.An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells.Proc Natl Acad Sci U S A，2003，100（8）：4633-4638.
80.Yauch RL，et al.A paracrine requirement for hedgehog signalling in cancer.Nature，2008，455（7211）：406-410.
81.Scales SJ，et al.Mechanisms of Hedgehog pathway activation in cancer and implications for therapy.Trends Pharmacol Sci，2009，30（6）：303-312.
82.Thompson MC，et al.Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations.J Clin Oncol，2006，24（12）：1924-1931.
83.Nolan-Stevaux O，et al.GLI1 is regulated through Smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation.Genes Dev，2009，23（1）：24-36.
84.Zhao C，et al.Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia.Nature，2009，458（7239）：776-779.
85.Dlugosz A，et al.Vismodegib.Nat Rev Drug Discov，2012，6（11）：437-438.
86.Sandhiya S，et al.The dawn of hedgehog inhibitors：Vismodegib.J Pharmacol Pharmacother，2013，4（1）：4-7.