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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma

Authors: Qi Zhou, Yafeng Wang, Baogang Peng, Lijian Liang, Jiaping Li

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Notch signaling, a critical pathway for tissue development, contributes to tumorigenesis in many tissues; however, the roles of Notch signaling in Intrahepatic Cholangiocarcinoma (ICC) remains unclear. In this study, we evaluated the expression and effects of Notch1 on cell migration in ICC.

Methods

Multiple cellular and molecular approaches were performed including gene transfection, siRNA transfection, RT-PCR, Western blotting, Rac activation assays and immunofluorescence.

Results

We found that Notch1 was up-regulated in ICC tissues and cell lines. The exogenous expression of Notch1 in glioma cells increased their migratory and invasive capacity. Similarly, the suppression of Notch1 expression inactivated Rac1 and inhibited ICC cell migration. Notch1 over expression induced an Epithelial-to-mesenchymal transition (EMT) phenotype that included enhanced expression of α-SMA and Vimentin, loss of E-cadherin expression, morphological changes and cytoskeletal reorganization in ICC cells.

Conclusion

Notch1 may induce a migratory effect in ICC by causing an epithelial-mesenchymal transition and activating Rac1 and could serve as a novel diagnostic and therapeutic target in patients with ICC.
Appendix
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Literature
1.
2.
Shaib YH, Davila JA, McGlynn K, El-Serag HB: Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?. J Hepatol. 2004, 40: 472-477. 10.1016/j.jhep.2003.11.030.CrossRefPubMed
3.
Olnes MJ, Erlich R: A review and update on cholangiocarcinoma. Oncology-Basel. 2004, 66: 167-179. 10.1159/000077991.CrossRef
4.
Yilmaz M, Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009, 28: 15-33. 10.1007/s10555-008-9169-0.CrossRefPubMed
5.
Penton AL, Leonard LD, Spinner NB: Notch signaling in human development and disease. Semin Cell Dev Biol. 2012, 23: 450-457. 10.1016/j.semcdb.2012.01.010.CrossRefPubMedPubMedCentral
6.
7.
8.
Dufraine J, Funahashi Y, Kitajewski J: Notch signaling regulates tumor angiogenesis by diverse mechanisms. Oncogene. 2008, 27: 5132-5137. 10.1038/onc.2008.227.CrossRefPubMedPubMedCentral
9.
Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH: Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer. 2006, 106: 2503-2513. 10.1002/cncr.21904.CrossRefPubMed
10.
Wang Z, Zhang Y, Banerjee S, Li Y, Sarkar FH: Inhibition of nuclear factor kappab activity by genistein is mediated via Notch-1 signaling pathway in pancreatic cancer cells. Int J Cancer. 2006, 118: 1930-1936. 10.1002/ijc.21589.CrossRefPubMed
11.
Shi TP, Xu H, Wei JF, Ai X, Ma X, Wang BJ, Ju ZH, Zhang GX, Wang C, Wu ZQ, Zhang X: Association of low expression of notch-1 and jagged-1 in human papillary bladder cancer and shorter survival. J Urol. 2008, 180: 361-366. 10.1016/j.juro.2008.02.037.CrossRefPubMed
12.
Reedijk M, Pinnaduwage D, Dickson BC, Mulligan AM, Zhang H, Bull SB, O'Malley FP, Egan SE, Andrulis IL: JAG1 expression is associated with a basal phenotype and recurrence in lymph node-negative breast cancer. Breast Cancer Res Treat. 2008, 111: 439-448. 10.1007/s10549-007-9805-3.CrossRefPubMed
13.
Zhu YM, Zhao WL, Fu JF, Shi JY, Pan Q, Hu J, Gao XD, Chen B, Li JM, Xiong SM, Gu LJ, Tang JY, Liang H, Jiang H, Xue YQ, Shen ZX, Chen Z, Chen SJ: NOTCH1 mutations in T-cell acute lymphoblastic leukemia: prognostic significance and implication in multifactorial leukemogenesis. Clin Cancer Res. 2006, 12: 3043-3049. 10.1158/1078-0432.CCR-05-2832.CrossRefPubMed
14.
Cruickshank SM, Southgate J, Selby PJ, Trejdosiewicz LK: Inhibition of T cell activation by normal human biliary epithelial cells. J Hepatol. 1999, 31: 1026-1033. 10.1016/S0168-8278(99)80315-8.CrossRefPubMed
15.
Jarzynka MJ, Hu B, Hui KM, Bar-Joseph I, Gu W, Hirose T, Haney LB, Ravichandran KS, Nishikawa R, Cheng SY: ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion. Cancer Res. 2007, 67: 7203-7211. 10.1158/0008-5472.CAN-07-0473.CrossRefPubMedPubMedCentral
16.
Chen J, Imanaka N, Chen J, Griffin JD: Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer. 2010, 102: 351-360. 10.1038/sj.bjc.6605486.CrossRefPubMed
17.
Mumm JS, Schroeter EH, Saxena MT, Griesemer A, Tian X, Pan DJ, Ray WJ, Kopan R: A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol Cell. 2000, 5: 197-206. 10.1016/S1097-2765(00)80416-5.CrossRefPubMed
18.
Weinmaster G: The ins and outs of notch signaling. Mol Cell Neurosci. 1997, 9: 91-102. 10.1006/mcne.1997.0612.CrossRefPubMed
19.
Dunwoodie SL, Henrique D, Harrison SM, Beddington RS: Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo. Development. 1997, 124: 3065-3076.PubMed
20.
Rao PK, Dorsch M, Chickering T, Zheng G, Jiang C, Goodearl A, Kadesch T, McCarthy S: Isolation and characterization of the notch ligand delta4. Exp Cell Res. 2000, 260: 379-386. 10.1006/excr.2000.5034.CrossRefPubMed
21.
Yoneya T, Tahara T, Nagao K, Yamada Y, Yamamoto T, Osawa M, Miyatani S, Nishikawa M: Molecular cloning of delta-4, a new mouse and human Notch ligand. J Biochem. 2001, 129: 27-34. 10.1093/oxfordjournals.jbchem.a002832.CrossRefPubMed
22.
Shutter JR, Scully S, Fan W, Richards WG, Kitajewski J, Deblandre GA, Kintner CR, Stark KL: Dll4, a novel Notch ligand expressed in arterial endothelium. Genes Dev. 2000, 14: 1313-1318.PubMedPubMedCentral
23.
Ranganathan P, Weaver KL, Capobianco AJ: Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer. 2011, 11: 338-351. 10.1038/nrc3035.CrossRefPubMed
24.
Koch U, Radtke F: Notch and cancer: a double-edged sword. Cell Mol Life Sci. 2007, 64: 2746-2762. 10.1007/s00018-007-7164-1.CrossRefPubMed
25.
Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C: Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg. 2009, 33: 1247-1254. 10.1007/s00268-009-9970-0.CrossRefPubMed
26.
27.
28.
Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002, 2: 442-454. 10.1038/nrc822.CrossRefPubMed
29.
Etienne-Manneville S, Hall A: Rho GTPases in cell biology. Nature. 2002, 420: 629-635. 10.1038/nature01148.CrossRefPubMed
30.
Lee TK, Poon RT, Yuen AP, Man K, Yang ZF, Guan XY, Fan ST: Rac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression. Clin Cancer Res. 2006, 12: 5082-5089. 10.1158/1078-0432.CCR-05-2794.CrossRefPubMed
31.
Jung HB, Sohn JH, Ji EK, Song H, Mook-Jung I: Rac1 changes the substrate specificity of γ-secretase between amyloid precursor protein and Notch1. Biochem Biophys Res Commun. 2008, 37: 913-917.CrossRef
Metadata
Title
The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma
Authors
Qi Zhou
Yafeng Wang
Baogang Peng
Lijian Liang
Jiaping Li
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-244

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