上皮-间充质转化对消化系统肿瘤及纤维化作用的研究进展

杨阳; 樊海宁; 邓勇

上皮-间充质转化对消化系统肿瘤及纤维化作用的研究进展

青海大学医学院附属医院肝胆胰外二科

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中图分类号: R575.2
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出版历程
- 出版日期: 2012-04-20

The role of epithelial-mesenchymal transition in gastrointestinal cancer and fibrosis

摘要

摘要: 上皮-间充质转化（EMT）是近年细胞生物学领域的重大发现;在生理学方面,EMT可引起胚胎形成、伤口愈合和组织再生。在病理学方面,能引起组织纤维化、肿瘤发生、发展、转移及耐药性的形成。目前对于EMT的相关研究正成为临床和基础研究领域十分活跃的课题,对于众多疾病的防治具有深远影响。近期一些研究阐明了EMT关于某些疾病的发病基础机制及其主要的调节因子。将EMT机制作为靶向治疗的药物治疗方案可被应用于预防组织纤维化及抑制肿瘤进展方面。在消化系统领域,有许多关于EMT在胃肠道肿瘤、肝脏肿瘤、胰腺肿瘤及肝纤维化方面起到关键性作用的证据。然而,EMT会在不同疾病中表现出不同的变化,而且在许多特殊疾病中EMT的调节因子尚待证实。本文将对目前关于EMT在消化系统领域肿瘤及纤维化方面作用的研究进展作一综述。
- 上皮-间充质转化 /
- 消化系统肿瘤 /
- 肝硬化
Abstract: The epithelial-mesenchymal transition (EMT) is a major discovery of cytobiology in recent years.It plays physiologic roles in the embryogenesis, wound healing, and tissue regeneration.In terms of pathological direction, it causes organ fibrosis, cancer development, progression, metastasis, and chemoresistance.The EMT-related research became a hot topic in clinical and basic research area which has a far-reaching influence on diseases prevention and control.Recently, the underlying mechanism of EMT and numerous EMT regulators have been identified.Pharmaceutical treatment strategies target EMT pathway could be applied for the prevention of tissue fibrosis and cancer progression.In the area of gastroenterology, profuse evidences have been collected about the critical roles of EMT in cancers of the gastrointestinal tract, liver, and pancreas and hepatic fibrosis.However, EMT varies widely among different cancer types, and much remains to be identified about the main regulators of EMT in a specific disease.In this review, we present recent researches regarding the roles of EMT in cancers and organic fibrosis in the area of gastroenterology.
- epithelial-mesenchymal transition /
- digestive system neoplasms /
- liver cirrhosis

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参考文献(42)

[1]Klymkowsky MW, Savagner P.Epithelial-mesenchymal transi-tion:a cancer researcher's conceptual friend and foe[J].Am JPathol, 2009, 174 (5) :1588-1593.

[2]Thiery JP, Acloque H, Huang RY, et al.Epithelial-mesen-chymal transitions in development and disease[J].Cell, 2009, 139 (5) :871-890.

[3]Zeisberg M, Neilson EG.Biomarkers for epithelial-mesenchy-mal transitions[J].J Clin Invest, 2009, 119:1429-1437.

[4]Cordon-Cardo C, Prives C.At the crossroads of inflamma-tion and tumorigenesis[J].J Exp Med, 1999, 190 (10) :1367-1370.

[5]Zhou Q, Zeng R, Xu C, et al.Erbin inhibits TGF-β1-in-duced EMT in renal tubular epithelial cells through an ERK-dependent pathway[J].J Mol Med (Berl) , 2011 Nov 25.

[6] Bracken CP, Gregory PA, Khew-Goodall Y, et al. The role of microRNAs in metastasis and epithelial-mesenchymal transition[J]. Cell Mol Life Sci, 2009, 66 (10) : 1682-1699.

[7] Natalwala A, Spychal R, Tselepis C. Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract[J]. World J Gastroenterol, 2008, 14 (24) : 3792-3797.

[8] Uchikado Y, Natsugoe S, Okumura H, et al. Slug expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma[J]. Clin Cancer Res, 2005, 11 (3) : 1174-1180.

[9] Natsugoe S, Uchikado Y, Okumura H, et al. Snail plays a key role in E-cadherin preserved esophageal squamous cell carcinoma[J]. Oncol Rep, 2007, 17 (3) : 517-523.

[10] Yuen HF, Chan YP, Wong ML, et al. Upregulation of Twist in esophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis[J]. J Clin Pathol, 2007, 60 (5) : 510-514.

[11]Rosivatz E, Becker KF, Kremmer E, et al.Expression andnuclear localization of Snail, an E-cadherin repressor, in ad-enocarcinomas of the upper gastrointestinal tract[J].Vir-chows Arch, 2006, 448 (3) :277-287.

[12] Jethwa P, Naqvi M, Hardy RG, et al. Overexpression of Slug is associated with malignant regression of esophageal adenocarcinoma[J]. World J Gastroenterol, 2008, 14 (7) : 1044-1052.

[13] Rosivatz E, Becker I, Specht K, et al. Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer[J]. Am J Pathol, 2002, 161 (5) : 1881-1891.

[14]Yang Z, Zhang X, Gang H, et al.Up-regulation of gastriccancer cell invasion by Twist is accompanied by N-cadherinand fibronectin expression[J].Biochem Biophys Res Com-mun, 2007, 358 (3) :925-930.

[15]Castro Alves C, Rosivatz E, Schott C, et al.Slug is overex-pressed in gastric carcinomas and may act synergisticallywith SIP1 and Snail in the down-regulation of E-cadherin[J].J Pathol, 2007, 211 (5) :507-515.

[16] Ohta H, Aoyagi K, Fukaya M, et al. Cross talk between hedgehog and epithelial-mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers[J]. Br J Cancer, 2009, 100 (2) : 389-398.

[17]Kim MA, Lee HS, Lee HE, et al.Prognostic importance ofepithelial-mesenchymal transition-related protein expres-sion in gastric carcinoma[J].Histopathology, 2009, 54 (4) :442-451.

[18]Yin Y, Grabowska AM, Clarke PA, et al.Helicobacter pyloripotentiates epithelial:mesenchymal transition in gastriccancer:links to soluble HB-EGF, gastrin and matrix metal-loproteinase-7[J].Gut, 2010, 59 (8) :1037-1045.

[19]Wheeler JM, Kim HC, Efstathiou JA, et al.Hypermethyla-tion of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer[J].Gut, 2001, 48 (3) :367-371.

[20]Roy HK, Smyrk TC, Koetsier J, et al.The transcriptional re-pressor SNAIL is overexpressed in human colon cancer[J].Dig Dis Sci, 2005, 50 (1) :42-46.

[21]Shioiri M, Shida T, Koda K, et al.Slug expression is an inde-pendent prognostic parameter for poor survival in colorectal car-cinoma patients[J].Br J Cancer, 2006, 94 (12) :1816-1822.

[22]Spaderna S, Schmalhofer O, Hlubek F, et al.A transient, EMT-linked loss of basement membranes indicates metas-tasis and poor survival in colorectal cancer[J].Gastroenter-ology, 2006, 131 (3) :830-840.

[23]Hong R, Choi DY, Lim SC, et al.The differential expressions ofthe epithelial-mesenchymal transition regulator, Slug and thecell adhesion molecule, E-cadherin in colorectal adenocarcino-ma[J].Korean J Pathol, 2008, 42:351-357.

[24] Jang TJ, Jeon KH, Jung KH. Cyclooxygenase-2 expression is related to the epithelial-to-mesenchymal transition in human colon cancers[J]. Yonsei Med J, 2009, 50 (6) : 818-824.

[25] Jiao W, Miyazaki K, Kitajima Y. Inverse correlation between E-cadherin and Snail expression in hepatocellular carcinoma cell lines in vitro and in vivo[J]. Br J Cancer, 2002, 86 (1) : 98-101.

[26]Sugimachi K, Tanaka S, Kameyama T, et al.Transcriptionalrepressor snail and progression of human hepatocellular carci-noma[J].Clin Cancer Res, 2003, 9 (7) :2657-2664.

[27]Miyoshi A, Kitajima Y, Sumi K, et al.Snail and SIP1 in-crease cancer invasion by upregulating MMP family in hepa-tocellular carcinoma cells[J].Br J Cancer, 2004, 90 (6) :1265-1273.

[28]Lee TK, Poon RT, Yuen AP, et al.Twist overexpression cor-relates with hepatocellular carcinoma metastasis through in-duction of epithelial-mesenchymal transition[J].Clin Canc-er Res, 2006, 12 (18) :5369-5376.

[29]Fransvea E, Angelotti U, Antonaci S, et al.Blocking trans-forming growth factor-beta up-regulates E-cadherin andreduces migration and invasion of hepatocellular carcinomacells[J].Hepatology, 2008, 47 (5) :1557-1566.

[30]Yang MH, Chen CL, Chau GY, et al.Comprehensive analy-sis of the independent effect of twist and snail in promotingmetastasis of hepatocellular carcinoma[J].Hepatology, 2009, 50 (5) :1464-1474.

[31]Battaglia S, Benzoubir N, Nobilet S, et al.Liver cancer-de-rived hepatitis C virus core proteins shift TGF-beta respon-ses from tumor suppression to epithelial-mesenchymal tran-sition[J].PLoS ONE, 2009, 4:e4355.

[32] Hotz B, Arndt M, Dullat S, et al. Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer[J]. Clin Cancer Res, 2007, 13 (16) : 4769-4776.

[33]Ohuchida K, Mizumoto K, Ohhashi S, et al.Twist, a noveloncogene, is upregulated in pancreatic cancer:clinical impli-cation of Twist expression in pancreatic juice[J].Int J Canc-er, 2007, 120 (8) :1634-1640.

[34]Imamichi Y, K o..nig A, Gress T, et al.Collagen type I-in-duced Smad-interacting protein 1 expression downregulatesE-cadherin in pancreatic cancer[J].Oncogene, 2007, 26 (16) :2381-2385.

[35] Shah AN, Summy JM, Zhang J, et al. Development and characterization of gemcitabine-resistant pancreatic tumor cells[J]. Ann Surg Oncol, 2007, 14: 3629-3637.

[36]Cates JM, Byrd RH, Fohn LE, et al.Epithelial-mesenchy-mal transition markers in pancreatic ductal adenocarcinoma[J].Pancreas, 2009, 38:e1-6.

[37]Wang Z, Li Y, Kong D, et al.Acquisition of epithelial-mes-enchymal transition phenotype of gemcitabine-resistantpancreatic cancer cells is linked with activation of the notchsignaling pathway[J].Cancer Res, 2009, 69 (6) :2400-2407.

[38] Choi SS, Diehl AM. Epithelial-to-mesenchymal transitions in the liver[J]. Hepatology, 2009, 50 (6) : 2007-2013.

[39]Zeisberg M, Yang C, Martino M, et al.Fibroblasts derivefrom hepatocytes in liver fibrosis via epithelial to mesenchy-mal transition[J].J Biol Chem, 2007, 282 (32) :23337-23347.

[40]Omenetti A, Porrello A, Jung Y, et al.Hedgehog signalingregulates epithelial-mesenchymal transition during biliary fi-brosis in rodents and humans[J].J Clin Invest, 2008, 118 (10) :3331-3342.

[41] Harada K, Sato Y, Ikeda H, et al. Epithelial-mesenchymal transition induced by biliary innate immunity contributes to the sclerosing cholangiopathy of biliary atresia[J]. J Pathol, 2009, 217 (5) : 654-664.

[42]Syn WK, Jung Y, Omenetti A, et al.Hedgehog-mediatedepithelial-to-mesenchymal transition and fibrogenic repairin nonalcoholic fatty liver disease[J].Gastroenterology, 2009, 137 (4) :1478-1488.

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