The dynamic roles of TGF‐β in cancer

Journal of Pathology - Tập 223 Số 2 - Trang 206-219 - 2011
Erik Meulmeester1, Peter ten Dijke1,2
1Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands
2Uppsala University and Ludwig Institute for Cancer Research, Box 595, 75124, Uppsala, Sweden

Tóm tắt

AbstractThe transforming growth factor‐β (TGF‐β) signalling pathway plays a critical and dual role in the progression of human cancer. During the early phase of tumour progression, TGF‐β acts as a tumour suppressor, exemplified by deletions or mutations in the core components of the TGF‐β signalling pathway. On the contrary, TGF‐β also promotes processes that support tumour progression such as tumour cell invasion, dissemination, and immune evasion. Consequently, the functional outcome of the TGF‐β response is strongly context‐dependent including cell, tissue, and cancer type. In this review, we describe the molecular signalling pathways employed by TGF‐β in cancer and how these, when perturbed, may lead to the development of cancer. Concomitantly with our increased appreciation of the molecular mechanisms that govern TGF‐β signalling, the potential to therapeutically target specific oncogenic sub‐arms of the TGF‐β pathway increases. Indeed, clinical trials with systemic TGF‐β signalling inhibitors for treatment of cancer patients have been initiated. However, considering the important role of TGF‐β in cardiovascular and many other tissues, careful screening of patients is warranted to minimize unwanted on‐target side effects. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Tài liệu tham khảo

10.1016/j.ceb.2009.01.021

10.1016/j.it.2010.04.002

10.1038/nrc2853

10.1016/j.cell.2008.07.001

10.1016/j.cytogfr.2005.09.009

10.1016/S0964-1955(96)00043-7

10.4049/jimmunol.143.3.877

10.1002/(SICI)1097-0045(19980915)37:1<19::AID-PROS4>3.0.CO;2-3

10.1016/S0959-8049(05)80116-9

Friedman E, 1995, High levels of transforming growth factor β1 correlate with disease progression in human colon cancer, Cancer Epidemiol Biomarkers Prev, 4, 549

Dalal BI, 1993, Immunocytochemical localization of secreted transforming growth factor‐β1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma, Am J Pathol, 143, 381

Picon A, 1998, A subset of metastatic human colon cancers expresses elevated levels of transforming growth factor β1, Cancer Epidemiol Biomarkers Prev, 7, 497

10.1002/jcp.10066

10.1111/j.1349-7006.2009.01441.x

10.1038/nri2808

10.1073/pnas.1633291100

10.1074/jbc.270.18.10618

10.1016/0092-8674(87)90192-9

10.1038/321779a0

10.1210/er.2004-0001

10.1016/S0092-8674(03)00432-X

10.1038/37284

10.1146/annurev.cellbio.21.022404.142018

10.1016/0092-8674(93)90368-Z

10.1016/S1097-2765(03)00386-1

10.1128/MCB.01192-08

10.1038/cr.2008.325

10.1016/S0092-8674(00)81600-1

10.1016/S0092-8674(00)81696-7

10.1128/MCB.01038-08

10.1111/j.1349-7006.2009.01299.x

10.1046/j.1432-1327.2000.01828.x

10.1016/j.ceb.2007.02.015

10.1016/S0092-8674(00)81701-8

10.1016/j.molcel.2009.10.028

10.1016/j.cell.2006.03.044

10.1074/jbc.M610172200

10.1101/gad.1384706

10.1038/70258

10.1016/j.molcel.2009.09.043

10.1016/j.cell.2008.10.051

10.1006/bbrc.1998.9170

10.1038/39369

10.1038/39355

10.1006/bbrc.1998.8200

10.1016/S0092-8674(00)80303-7

10.1101/gad.12.2.186

10.1016/S1097-2765(00)00134-9

10.1074/jbc.C100008200

10.1074/jbc.273.44.29195

10.1016/j.ygyno.2004.10.006

10.1007/BF03345213

10.1126/science.286.5440.771

10.1101/gad.13.17.2196

10.1101/gad.13.4.412

10.1074/jbc.274.49.35269

10.1158/0008-5472.CAN-04-0018

10.1242/dev.125.8.1433

10.1016/j.cell.2006.03.045

10.1073/pnas.0712044105

10.1038/35078562

10.1038/ncb1117

10.1128/MCB.24.5.2169-2180.2004

10.1016/j.cytogfr.2009.10.004

10.1101/gad.1166904

10.1101/gad.1360605

10.1016/j.molcel.2008.09.002

10.1016/j.cellsig.2009.05.012

10.1091/mbc.12.1.27

10.1038/sj.emboj.7601818

10.1126/science.1105718

10.1038/ncb2022

10.1038/nature02006

10.1126/science.7761852

Grady WM, 1999, Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers, Cancer Res, 59, 320

10.1016/S0304-3835(96)04583-1

Wang D, 2000, Analysis of specific gene mutations in the transforming growth factor‐β signal transduction pathway in human ovarian cancer, Cancer Res, 60, 4507

Goggins M, 1998, Genetic alterations of the transforming growth factor β receptor genes in pancreatic and biliary adenocarcinomas, Cancer Res, 58, 5329

Chen T, 1998, Transforming growth factor β type I receptor kinase mutant associated with metastatic breast cancer, Cancer Res, 58, 4805

10.1158/0008-5472.CAN-04-3272

10.1101/gad.1413306

10.1101/gad.1475506

10.1158/0008-5472.CAN-06-0890

10.1016/j.ccr.2007.08.020

10.1101/gad.1478706

10.1016/S0092-8674(00)81132-0

10.1073/pnas.0605333103

10.1016/S0092-8674(04)00298-3

10.1074/jbc.M909467199

10.1073/pnas.92.12.5545

10.1038/371257a0

10.1038/nrc1208

10.1073/pnas.0406771101

10.1038/35070076

10.1038/nature01119

10.1016/S1535-6108(03)00141-7

10.1038/emboj.2009.291

10.1038/ncb731

10.1128/MCB.25.22.10017-10028.2005

10.1074/jbc.M307869200

10.1091/mbc.E03-04-0201

Sakakura T, 1981, Accelerated mammary cancer development by fetal salivary mesenchyma isografted to adult mouse mammary epithelium, J Natl Cancer Inst, 66, 953

10.1091/mbc.10.4.1221

10.1126/science.1090922

10.1038/sj.onc.1208685

10.1016/j.ccr.2009.12.043

Myeroff LL, 1995, A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability, Cancer Res, 55, 5545

Parsons R, 1995, Microsatellite instability and mutations of the transforming growth factor β type II receptor gene in colorectal cancer, Cancer Res, 55, 5548

Schutte M, 1996, DPC4 gene in various tumor types, Cancer Res, 56, 2527

10.1126/science.271.5247.350

10.1006/bbrc.1996.0934

10.1517/14728220802705696

10.1023/A:1005863419880

Takenoshita S, 1998, Absence of mutations in the analysis of coding sequences of the entire transforming growth factor‐β type II receptor gene in sporadic human breast cancers, Oncol Rep, 5, 367

10.1111/j.1365-2559.2006.02551.x

10.1172/JCI39104

10.1158/0008-5472.CAN-05-0699

10.1111/j.1349-7006.2007.00550.x

10.1038/cr.2009.5

10.1007/s10585-007-9114-6

10.1016/j.ceb.2005.08.001

10.1083/jcb.127.6.2021

10.1158/0008-5472.CAN-05-3560

10.1091/mbc.E04-08-0658

10.1158/1541-7786.MCR-08-0558

10.1242/jcs.112.24.4557

10.4161/cc.7.20.6851

10.1038/ng1295-409

10.1038/ng1295-415

10.1242/dev.124.13.2659

10.1016/S0092-8674(00)80127-0

Hoot KE, 2008, Keratinocyte‐specific Smad2 ablation results in increased epithelial–mesenchymal transition during skin cancer formation and progression, J Clin Invest, 118, 2722

10.1016/j.ccr.2007.01.013

10.1016/j.cell.2008.03.027

10.1016/j.stem.2009.08.018

10.1038/nrc2622

10.1016/j.coph.2010.06.003

10.1016/S1535-6108(03)00132-6

10.1038/nature03799

10.1038/nrc1098

10.1158/1078-0432.CCR-0320-03

10.1172/JCI30740

10.1128/MCB.23.23.8691-8703.2003

10.1073/pnas.0932636100

10.1038/ncb1973

10.1172/JCI118947

10.1172/JCI3523

10.1359/jbmr.2002.17.9.1667

10.1158/1535-7163.MCT-07-0234

10.1073/pnas.0506517102

10.1038/onc.2009.426

10.1016/j.cell.2008.01.046

10.1073/pnas.87.4.1486

10.1038/nm1001-1118

10.1038/labinvest.2008.123

10.1016/j.ccr.2005.10.012

10.1172/JCI116871

10.1084/jem.20051511

10.4049/jimmunol.172.12.7335

10.1073/pnas.0730640100

10.1158/0008-5472.CAN-09-2123

10.1158/0008-5472.CAN-04-1627

10.1016/0378-1119(94)90408-1

10.1007/s002620100197

10.1089/oli.2006.0053

10.1007/978-3-540-71279-4_16

10.1172/JCI0215234

10.1172/JCI200215333

Rowland‐Goldsmith MA, 2002, Soluble type II transforming growth factor‐β receptor attenuates expression of metastasis‐associated genes and suppresses pancreatic cancer cell metastasis, Mol Cancer Ther, 1, 161

10.1038/sj.onc.1205439

10.4049/jimmunol.142.5.1536

10.1158/0008-5472.CAN-06-0068

10.1124/mol.62.1.65

10.1158/1535-7163.737.3.6

Matsuyama S, 2003, SB‐431542 and Gleevec inhibit transforming growth factor‐β‐induced proliferation of human osteosarcoma cells, Cancer Res, 63, 7791

10.1158/0008-5472.CAN-04-1013

10.1158/1078-0432.CCR-06-0162

10.1111/j.1349-7006.2006.00357.x

10.1038/sj.bjc.6605561

10.1158/1535-7163.MCT-07-0337

10.1016/j.canlet.2008.11.035

10.1016/j.ejca.2007.10.008

10.1158/1078-0432.CCR-06-0952

10.1158/1078-0432.CCR-07-1157

10.1038/nmeth.1446

10.1373/clinchem.2009.137158

10.1038/35000501

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Journal of Pathology

Tập 223 Số 2

206-219

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