Dysregulation of Wnt/β-Catenin Signaling in Gastrointestinal Cancers

被引：445

作者：

White, Bryan D. ^{[1
]}

Chien, Andy J. ^{[2
]}

Dawson, David W. ^{[3
]}

机构：

[1] Univ Washington, Sci & Technol Program, Bothell, WA USA

[2] Univ Washington, Sch Med, Dept Med, Div Dermatol,Inst Stem Cell & Regenerat Med, Seattle, WA 98195 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

来源：

GASTROENTEROLOGY | 2012年 / 142卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Wnt; beta-catenin; Colorectal Carcinoma; Hepatocellular Carcinoma; Pancreatic Ductal Ddenocarcinoma; HUMAN HEPATOCELLULAR CARCINOMAS; PANCREATIC DUCTAL ADENOCARCINOMA; HEPATOCYTE GROWTH-FACTOR; BETA-CATENIN; COLORECTAL-CANCER; STEM-CELLS; E-CADHERIN; GENE-MUTATIONS; POOR-PROGNOSIS; NUCLEAR TRANSLOCATION;

D O I：

10.1053/j.gastro.2011.12.001

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Wnt/beta-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, adenomatous polyposis coli, and Wnt/beta-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/beta-catenin signaling is also modulated through various other mechanisms in cancer, including cross talk with other altered signaling pathways. A more complex view of Wnt/beta-catenin signaling and its role in gastrointestinal cancers is now emerging as divergent phenotypic outcomes are found to be dictated by temporospatial context and relative levels of pathway activation. This review summarizes the dysregulation of Wnt/beta-catenin signaling in colorectal carcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, with particular emphasis on the latter two. We conclude by addressing some of the major challenges faced in attempting to target the pathway in the clinic.

引用

页码：219 / 232

页数：14

共 140 条

[1] The 'just-right' signaling model:: APC somatic mutations are selected based on a specific level of activation of the β-catenin signaling cascade [J].

Albuquerque, C ;

Breukel, C ;

van der Luijt, R ;

Fidalgo, P ;

Lage, P ;

Slors, FJM ;

Leitao, CN ;

Fodde, R ;

Smits, R .

HUMAN MOLECULAR GENETICS, 2002, 11 (13) :1549-1560

[2] Proximal events in Wnt signal transduction [J].

Angers, Stephane ;

Moon, Randall T. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (07) :468-477

[3] Reduced Level of Smoothened Suppresses Intestinal Tumorigenesis by Down-Regulation of Wnt Signaling [J].

Arimura, Sumimasa ;

Matsunaga, Akihiro ;

Kitamura, Takanori ;

Aoki, Koji ;

Aoki, Masahiro ;

Taketo, Makoto M. .

GASTROENTEROLOGY, 2009, 137 (02) :629-638

[4] Chemical-Genetic Screen Identifies Riluzole as an Enhancer of Wnt/β-catenin Signaling in Melanoma [J].

Biechele, Travis L. ;

Camp, Nathan D. ;

Fass, Daniel M. ;

Kulikauskas, Rima M. ;

Robin, Nick C. ;

White, Bryan D. ;

Taraska, Corinne M. ;

Moore, Erin C. ;

Muster, Jeanot ;

Karmacharya, Rakesh ;

Haggarty, Stephen J. ;

Chien, Andy J. ;

Moon, Randall T. .

CHEMISTRY & BIOLOGY, 2010, 17 (11) :1177-1182

[5] SMAD4 Gene Mutations Are Associated with Poor Prognosis in Pancreatic Cancer [J].

Blackford, Amanda ;

Serrano, Oscar K. ;

Wolfgang, Christopher L. ;

Parmigiani, Giovanni ;

Jones, Sian ;

Zhang, Xiaosong ;

Parsons, D. Williams ;

Lin, Jimmy Cheng-Ho ;

Leary, Rebecca J. ;

Eshleman, James R. ;

Goggins, Michael ;

Jaffee, Elizabeth M. ;

Iacobuzio-Donahue, Christine A. ;

Maitra, Anirban ;

Cameron, John L. ;

Olino, Kelly ;

Schulick, Richard ;

Winter, Jordan ;

Herman, Joseph M. ;

Laheru, Daniel ;

Klein, Alison P. ;

Vogelstein, Bert ;

Kinzler, Kenneth W. ;

Velculescu, Victor E. ;

Hruban, Ralph H. .

CLINICAL CANCER RESEARCH, 2009, 15 (14) :4674-4679

[6] Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets [J].

Boyault, Sandrine ;

Rickman, David S. ;

de Reynies, Aurelien ;

Balabaud, Charles ;

Rebouissou, Sandra ;

Jeannot, Emmanuelle ;

Herault, Aurelie ;

Saric, Jean ;

Belghiti, Jacques ;

Franco, Dominique ;

Bioulac-Sage, Paulette ;

Laurent-Puig, Pierre ;

Zucman-Rossi, Jessica .

HEPATOLOGY, 2007, 45 (01) :42-52

[7] Gastrointestinal stem cells in development and cancer [J].

Brabletz, S. ;

Schmalhofer, O. ;

Brabletz, T. .

JOURNAL OF PATHOLOGY, 2009, 217 (02) :307-317

[8] Nuclear overexpression of the oncoprotein β-catenin in colorectal cancer is localized predominantly at the invasion front [J].

Brabletz, T ;

Jung, A ;

Hermann, K ;

Gunther, K ;

Hohenberger, W ;

Kirchner, T .

PATHOLOGY RESEARCH AND PRACTICE, 1998, 194 (10) :701-704

[9] Genetic Dissection of Differential Signaling Threshold Requirements for the Wnt/β-Catenin Pathway In Vivo [J].

Buchert, Michael ;

Athineos, Dimitris ;

Abud, Helen E. ;

Burke, Zoe D. ;

Faux, Maree C. ;

Samuel, Michael S. ;

Jarnicki, Andrew G. ;

Winbanks, Catherine E. ;

Newton, Ian P. ;

Meniel, Valerie S. ;

Suzuki, Hiromu ;

Stacker, Steven A. ;

Nathke, Inke S. ;

Tosh, David ;

Huelsken, Joerg ;

Clarke, Alan R. ;

Heath, Joan K. ;

Sansom, Owen J. ;

Ernst, Matthias .

PLOS GENETICS, 2010, 6 (01)

[10]

Cadoret A, 2001, CANCER RES, V61, P3245

← 1 2 3 4 5 6 7 8 9 10 →