Research Progress on Notch Signaling Pathway in Digestive Tumors_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GAI Dawei ¹ , GUO Lingyun ¹ , LIU Tao ² ,  LI Yumin ²

1.Departmeng of The Second Clinical Medical College of Lanzhou University， Lanzhou 730030， Gansu Province， China;;
2.The Second Hospital of Lanzhou University， Key Laboratory of Digestive System Tumors， Lanzhou 730030， Gansu Province， China;

Corresponding author：

LI Yumin, Email: liym@lzu.edu.cn

Keywords：

Notch signaling pathway; Digestive tumors; Epithelial-mesenchymal transition

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the structure characteristics， functions， and research progress of Notch signaling pathway in digestive tumors.
Methods 　The related literatures about the molecular genetic mechanism of Notch signaling pathway were reviewed.
Results 　The Notch signaling pathway plays an important role not only in normal cells’ growth， differentiation， proliferation， and apoptosis but also in a variety of tumors’ occurrence and development.
Conclusion 　The reasonable regulation to Notch signaling pathway may open up new ways to the treatment of the tumor.

Citation： GAI Dawei,GUO Lingyun,LIU Tao,LI Yumin. Research Progress on Notch Signaling Pathway in Digestive Tumors. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(10): 1188-1192. doi: Copy

1.	Artavanis-Tsakonas S， Matsuno K， Fortini ME. Notch signaling[J]. Science， 1995， 268(5208)： 225-232.
2.	Mumm JS， Kopan R. Notch signaling：from the outside in[J]. Dev Biol， 2000， 228(2)：151-165.
3.	South AP， Cho RJ， Aster JC. The double-edged sword of Notch signaling in cancer[J]. Semin Cell Dev Biol， 2012， 23(4)：458-464.
4.	Ranganathan P， Weaver KL， Capobianco AJ. Notch signalling in solid tumours： a little bit of everything but not all the time[J]. Nat Rev Cancer， 2011， 11(5)：338-351.
5.	Apelqvist A， Li H， Sommer L， et al. Notch signalling controls pancreatic cell differentiation[J]. Nature， 1999， 400(6747)：877-881.
6.	Bray SJ. Notch signalling：a simple pathway becomes complex[J]. Nat Rev Mol Cell Biol， 2006， 7(9)：678-689.
7.	Jarriault S， Brou C， Logeat F， et al. Signalling downstream of activated mammalian Notch[J]. Nature， 1995， 377(6547)：355-358.
8.	Burstein HJ， Schwartz RS. Molecular origins of cancer[J]. N Engl J Med， 2008， 358(5)：527.
9.	Hu YY， Zheng MH， Zhang R， et al. Notch signaling pathway and cancer metastasis[J]. Adv Exp Med Biol， 2012， 727：186-198.
10.	Phillips HS， Kharbanda S， Chen R， et al. Molecular subclasses of high-grade glioma predict prognosis， delineate a pattern of disease progression， and resemble stages in neurogenesis[J]. Cancer Cell， 2006， 9(3)：157-173.
11.	Schroeter EH， Kisslinger JA， Kopan R. Notch-1 signallingrequires ligand-induced proteolytic release of intracellular domain[J]. Nature， 1998， 393(6683)：382-386.
12.	Fan X， Mikolaenko I， Elhassan I， et al. Notch1 and notch2 have opposite effects on embryonal brain tumor growth[J]. Cancer Res， 2004， 64(21)：7787-7793.
13.	Dang TP， Gazdar AF， Virmani AK， et al. Chromosome 19 translocation， overexpression of Notch3， and human lung cancer[J]. J Natl Cancer Inst， 2000， 92(16)：1355-1357.
14.	Park JT， Li M， Nakayama K， et al. Notch3 gene amplification in ovarian cancer[J]. Cancer Res， 2006， 66(12)：6312-6318.
15.	Reedijk M， Odorcic S， Chang L， et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival[J]. Cancer Res， 2005， 65(18)：8530-8537.
16.	Proweller A， Tu L， Lepore JJ， et al. Impaired notch signaling promotes de novo squamous cell carcinoma formation[J]. CancerRes， 2006， 66(15)：7438-7444.
17.	Sekine A， Akiyama Y， Yanagihara K， et al. Hath1 up-regulates gastric mucin gene expression in gastric cells[J]. Biochem BiophysRes Commun， 2006， 344(4)：1166-1171.
18.	Tamagawa Y， Ishimura N， Uno G， et al. Notch signaling pathwayand Cdx2 expression in the development of Barrett’s esophagus[J].Lab Invest， 2012， 92(6)：896-909.
19.	Zhou BB， Zhang H， Damelin M， et al. Tumour-initiating cells：challenges and opportunities for anticancer drug discovery[J]. Nat Rev Drug Discov， 2009， 8(10)：806-823.
20.	Snijders AM， Schmidt BL， Fridlyand J， et al. Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma[J]. Oncogene， 2005， 24(26)：4232-4242.
21.	Leethanakul C， Patel V， Gillespie J， et al. Distinct pattern ofexpression of differentiation and growth-related genes in squamouscell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays[J]. Oncogene， 2000， 19(28)：3220-3224.
22.	Sekine A， Akiyama Y， Yanagihara K， et al. Hath1 up-regulates gastric mucin gene expression in gastric cells[J]. Biochem BiophysRes Commun， 2006， 344(4)：1166-1171.
23.	Yeh TS， Wu CW， Hsu KW， et al. The activated Notch1 signal pathway is associated with gastric cancer progression throughcyclooxygenase-2[J]. Cancer Res， 2009， 69(12)：5039-5048.
24.	Mills JC， Shivdasani RA. Gastric epithelial stem cells[J]. Gastroenterology， 2011， 140(2)：412-424.
25.	Fan R， Chen P， Zhao D， et al. Cooperation of deregulated Notch signaling and Ras pathway in human hepatocarcinogenesis[J]. J Mol Histol， 2011， 42(5)：473-481.
26.	Qi R， An H， Yu Y， et al. Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis[J]. Cancer Res， 2003， 63(23)：8323-8329.
27.	Yao Z， Mishra L. Cancer stem cells and hepatocellular carcinoma[J]. Cancer Biol Ther， 2009， 8(18)：1691-1698.
28.	Wang M， Xue L， Cao Q， et al. Expression of Notch1， Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma[J]. Neoplasma， 2009， 56(6)：533-541.
29.	Sonoshita M， Aoki M， Fuwa H， et al. Suppression of colon cancermetastasis by Aes through inhibition of Notch signaling[J]. Cancer Cell， 2011， 19(1)：125-137.
30.	Yabuuchi S， Pai SG， Campbell NR， et al. Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer[J]. Cancer Lett， 2013， 335(1)：41-51.
31.	Avila JL， Kissil JL. Notch signaling in pancreatic cancer：oncogene or tumor suppressor?[J]. Trends Mol Med， 2013， 19(5)：320-327.
32.	Miyamoto Y， Maitra A， Ghosh B， et al. Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatictumorigenesis[J]. Cancer Cell， 2003， 3(6)：565-576.
33.	Mullendore ME， Koorstra JB， Li YM， et al. Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer[J]. Clin Cancer Res， 2009， 15(7)：2291-2301.
34.	Mazur PK， Einwachter H， Lee M， et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and developmentof pancreatic ductal adenocarcinoma[J]. Proc Natl Acad Sci U S A， 2010， 107(30)：13438-13443.
35.	Hruban RH， Wilentz RE， Goggins M， et al. Pathology of incipientpancreatic cancer[J]. Ann Oncol， 1999， 10 Suppl 4：9-11.
36.	Walther A， Johnstone E， Swanton C， et al. Genetic prognostic and predictive markers in colorectal cancer[J]. Nat Rev Cancer， 2009， 9(7)：489-499.
37.	Yin L， Velazquez OC， Liu ZJ. Notch signaling： emerging mole-cular targets for cancer therapy[J]. Biochem Pharmacol， 2010， 80(5)：690-701.
38.	Konsavage WJ， Kyler SL， Rennoll SA， et al. Wnt/beta-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells[J]. J Biol Chem， 2012， 287(15)：11730-11739.
39.	Zhang H， Ye Y， Bai Z， et al. The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells is associated with the Delta1/Notch1 pathway[J]. Dig Dis Sci， 2008， 53(8)：2195-2203.
40.	Yeung TM， Gandhi SC， Bodmer WF. Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells[J]. Proc Natl Acad Sci U S A， 2011， 108(11)：4382-4387.
41.	Wilson BJ， Schatton T， Frank MH， et al. Colorectal cancer stem cells： biology and therapeutic implications[J]. Curr Colorectal Cancer Rep， 2011， 7(2)：128-135.
42.	Yasui H， Hideshima T， Richardson PG， et al. Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma[J]. Br J Haematol， 2006， 132(4)：385-397.
43.	Iso T， Maeno T， Oike Y， et al. Dll4-selective Notch signalinginduces ephrinB2 gene expression in endothelial cells[J]. BiochemBiophys Res Commun， 2006， 341(3)：708-714.
44.	Wu Y， Cain-Hom C， Choy L， et al. Therapeutic antibody targetingof individual Notch receptors[J]. Nature， 2010， 464(7291)：1052-1057.
45.	Katoh M， Katoh M. Bioinformatics for cancer management in the post-genome era[J]. Technol Cancer Res Treat， 2006， 5(2)：169-175.
46.	Hyde LA， Mchugh NA， Chen J， et al. Studies to investigate thein vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3， 5-difluorophenyl)-2-hydroxyethanoyl]-N1- [(7S)-5-methyl-6-oxo-6， 7-di hydro-5H-dibenzo[b， d]azepin-7-yl]-L-alaninamide (LY411， 575) in the CRND8 mouse[J]. J PharmacolExp Ther， 2006， 319(3)：1133-1143.

1. Artavanis-Tsakonas S， Matsuno K， Fortini ME. Notch signaling[J]. Science， 1995， 268(5208)： 225-232.
2. Mumm JS， Kopan R. Notch signaling：from the outside in[J]. Dev Biol， 2000， 228(2)：151-165.
3. South AP， Cho RJ， Aster JC. The double-edged sword of Notch signaling in cancer[J]. Semin Cell Dev Biol， 2012， 23(4)：458-464.
4. Ranganathan P， Weaver KL， Capobianco AJ. Notch signalling in solid tumours： a little bit of everything but not all the time[J]. Nat Rev Cancer， 2011， 11(5)：338-351.
5. Apelqvist A， Li H， Sommer L， et al. Notch signalling controls pancreatic cell differentiation[J]. Nature， 1999， 400(6747)：877-881.
6. Bray SJ. Notch signalling：a simple pathway becomes complex[J]. Nat Rev Mol Cell Biol， 2006， 7(9)：678-689.
7. Jarriault S， Brou C， Logeat F， et al. Signalling downstream of activated mammalian Notch[J]. Nature， 1995， 377(6547)：355-358.
8. Burstein HJ， Schwartz RS. Molecular origins of cancer[J]. N Engl J Med， 2008， 358(5)：527.
9. Hu YY， Zheng MH， Zhang R， et al. Notch signaling pathway and cancer metastasis[J]. Adv Exp Med Biol， 2012， 727：186-198.
10. Phillips HS， Kharbanda S， Chen R， et al. Molecular subclasses of high-grade glioma predict prognosis， delineate a pattern of disease progression， and resemble stages in neurogenesis[J]. Cancer Cell， 2006， 9(3)：157-173.
11. Schroeter EH， Kisslinger JA， Kopan R. Notch-1 signallingrequires ligand-induced proteolytic release of intracellular domain[J]. Nature， 1998， 393(6683)：382-386.
12. Fan X， Mikolaenko I， Elhassan I， et al. Notch1 and notch2 have opposite effects on embryonal brain tumor growth[J]. Cancer Res， 2004， 64(21)：7787-7793.
13. Dang TP， Gazdar AF， Virmani AK， et al. Chromosome 19 translocation， overexpression of Notch3， and human lung cancer[J]. J Natl Cancer Inst， 2000， 92(16)：1355-1357.
14. Park JT， Li M， Nakayama K， et al. Notch3 gene amplification in ovarian cancer[J]. Cancer Res， 2006， 66(12)：6312-6318.
15. Reedijk M， Odorcic S， Chang L， et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival[J]. Cancer Res， 2005， 65(18)：8530-8537.
16. Proweller A， Tu L， Lepore JJ， et al. Impaired notch signaling promotes de novo squamous cell carcinoma formation[J]. CancerRes， 2006， 66(15)：7438-7444.
17. Sekine A， Akiyama Y， Yanagihara K， et al. Hath1 up-regulates gastric mucin gene expression in gastric cells[J]. Biochem BiophysRes Commun， 2006， 344(4)：1166-1171.
18. Tamagawa Y， Ishimura N， Uno G， et al. Notch signaling pathwayand Cdx2 expression in the development of Barrett’s esophagus[J].Lab Invest， 2012， 92(6)：896-909.
19. Zhou BB， Zhang H， Damelin M， et al. Tumour-initiating cells：challenges and opportunities for anticancer drug discovery[J]. Nat Rev Drug Discov， 2009， 8(10)：806-823.
20. Snijders AM， Schmidt BL， Fridlyand J， et al. Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma[J]. Oncogene， 2005， 24(26)：4232-4242.
21. Leethanakul C， Patel V， Gillespie J， et al. Distinct pattern ofexpression of differentiation and growth-related genes in squamouscell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays[J]. Oncogene， 2000， 19(28)：3220-3224.
22. Sekine A， Akiyama Y， Yanagihara K， et al. Hath1 up-regulates gastric mucin gene expression in gastric cells[J]. Biochem BiophysRes Commun， 2006， 344(4)：1166-1171.
23. Yeh TS， Wu CW， Hsu KW， et al. The activated Notch1 signal pathway is associated with gastric cancer progression throughcyclooxygenase-2[J]. Cancer Res， 2009， 69(12)：5039-5048.
24. Mills JC， Shivdasani RA. Gastric epithelial stem cells[J]. Gastroenterology， 2011， 140(2)：412-424.
25. Fan R， Chen P， Zhao D， et al. Cooperation of deregulated Notch signaling and Ras pathway in human hepatocarcinogenesis[J]. J Mol Histol， 2011， 42(5)：473-481.
26. Qi R， An H， Yu Y， et al. Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis[J]. Cancer Res， 2003， 63(23)：8323-8329.
27. Yao Z， Mishra L. Cancer stem cells and hepatocellular carcinoma[J]. Cancer Biol Ther， 2009， 8(18)：1691-1698.
28. Wang M， Xue L， Cao Q， et al. Expression of Notch1， Jagged1 and beta-catenin and their clinicopathological significance in hepatocellular carcinoma[J]. Neoplasma， 2009， 56(6)：533-541.
29. Sonoshita M， Aoki M， Fuwa H， et al. Suppression of colon cancermetastasis by Aes through inhibition of Notch signaling[J]. Cancer Cell， 2011， 19(1)：125-137.
30. Yabuuchi S， Pai SG， Campbell NR， et al. Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer[J]. Cancer Lett， 2013， 335(1)：41-51.
31. Avila JL， Kissil JL. Notch signaling in pancreatic cancer：oncogene or tumor suppressor?[J]. Trends Mol Med， 2013， 19(5)：320-327.
32. Miyamoto Y， Maitra A， Ghosh B， et al. Notch mediates TGF alpha-induced changes in epithelial differentiation during pancreatictumorigenesis[J]. Cancer Cell， 2003， 3(6)：565-576.
33. Mullendore ME， Koorstra JB， Li YM， et al. Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer[J]. Clin Cancer Res， 2009， 15(7)：2291-2301.
34. Mazur PK， Einwachter H， Lee M， et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and developmentof pancreatic ductal adenocarcinoma[J]. Proc Natl Acad Sci U S A， 2010， 107(30)：13438-13443.
35. Hruban RH， Wilentz RE， Goggins M， et al. Pathology of incipientpancreatic cancer[J]. Ann Oncol， 1999， 10 Suppl 4：9-11.
36. Walther A， Johnstone E， Swanton C， et al. Genetic prognostic and predictive markers in colorectal cancer[J]. Nat Rev Cancer， 2009， 9(7)：489-499.
37. Yin L， Velazquez OC， Liu ZJ. Notch signaling： emerging mole-cular targets for cancer therapy[J]. Biochem Pharmacol， 2010， 80(5)：690-701.
38. Konsavage WJ， Kyler SL， Rennoll SA， et al. Wnt/beta-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells[J]. J Biol Chem， 2012， 287(15)：11730-11739.
39. Zhang H， Ye Y， Bai Z， et al. The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells is associated with the Delta1/Notch1 pathway[J]. Dig Dis Sci， 2008， 53(8)：2195-2203.
40. Yeung TM， Gandhi SC， Bodmer WF. Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells[J]. Proc Natl Acad Sci U S A， 2011， 108(11)：4382-4387.
41. Wilson BJ， Schatton T， Frank MH， et al. Colorectal cancer stem cells： biology and therapeutic implications[J]. Curr Colorectal Cancer Rep， 2011， 7(2)：128-135.
42. Yasui H， Hideshima T， Richardson PG， et al. Novel therapeutic strategies targeting growth factor signalling cascades in multiple myeloma[J]. Br J Haematol， 2006， 132(4)：385-397.
43. Iso T， Maeno T， Oike Y， et al. Dll4-selective Notch signalinginduces ephrinB2 gene expression in endothelial cells[J]. BiochemBiophys Res Commun， 2006， 341(3)：708-714.
44. Wu Y， Cain-Hom C， Choy L， et al. Therapeutic antibody targetingof individual Notch receptors[J]. Nature， 2010， 464(7291)：1052-1057.
45. Katoh M， Katoh M. Bioinformatics for cancer management in the post-genome era[J]. Technol Cancer Res Treat， 2006， 5(2)：169-175.
46. Hyde LA， Mchugh NA， Chen J， et al. Studies to investigate thein vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3， 5-difluorophenyl)-2-hydroxyethanoyl]-N1- [(7S)-5-methyl-6-oxo-6， 7-di hydro-5H-dibenzo[b， d]azepin-7-yl]-L-alaninamide (LY411， 575) in the CRND8 mouse[J]. J PharmacolExp Ther， 2006， 319(3)：1133-1143.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Progress on Notch Signaling Pathway in Digestive Tumors

Abstract Full text Figures/Tables Video References Cited by

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