The TGF-β paradox in human cancer: an update

被引：170

作者：

Tian, Maozhen ^{[1
]}

Schiemann, William P. ^{[1
]}

机构：

[1] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA

来源：

FUTURE ONCOLOGY | 2009年 / 5卷 / 02期

关键词：

angiogenesis; cancer; cell invasion; epithelial-mesenchymal transition; metastasis; signal transduction; transforming growth factor-beta; GROWTH-FACTOR-BETA; HEREDITARY HEMORRHAGIC TELANGIECTASIA; EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; BREAST-CANCER; LYSYL OXIDASE; TRANSFORMING GROWTH-FACTOR-BETA-1; SIGNALING PATHWAYS; TUMOR-GROWTH; T-CELLS;

D O I：

10.2217/14796694.5.2.259

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

TGF-beta plays an essential role in maintaining tissue homeostasis through its ability to induce cell cycle arrest, differentiation and apoptosis, and to preserve genomic stability. Thus, TGF-beta is a potent anticancer agent that prohibits the uncontrolled proliferation of epithelial, endothelial and hematopoietic cells. Interestingly, tumorigenesis typically elicits aberrations in the TGF-beta signaling pathway that engenders resistance to the cytostatic activities of TGF-beta, thereby enhancing the development and progression of human malignancies. Moreover, these genetic and epigenetic events conspire to convert TGF-beta from a suppressor of tumor formation to a promoter of their growth, invasion and metastasis. The dichotomous nature of TGF-beta during tumorigenesis is known as the 'TGF-beta paradox', which remains the most critical and mysterious question concerning the physiopathological role of this multifunctional cytokine. Here we review recent findings that directly impact our understanding of the TGF-beta paradox and discuss their importance to targeting the oncogenic activities of TGF-beta in developing and progressing neoplasms.

引用

页码：259 / 271

页数：13

共 140 条

[11] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].

Ben-Porath, Ittai ;

Thomson, Matthew W. ;

Carey, Vincent J. ;

Ge, Ruping ;

Bell, George W. ;

Regev, Aviv ;

Weinberg, Robert A. .

NATURE GENETICS, 2008, 40 (05) :499-507

[12] The activin receptor-like kinase 1 gene: Genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2 [J].

Berg, JN ;

Gallione, CJ ;

Stenzel, TT ;

Johnson, DW ;

Allen, WP ;

Schwartz, CE ;

Jackson, CE ;

Porteous, MEM ;

Marchuk, DA .

AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (01) :60-67

[13] Transforming growth factor-β signal transduction in angiogenesis and vascular disorders [J].

Bertolino, P ;

Deckers, M ;

Lebrin, F ;

ten Dijke, P .

CHEST, 2005, 128 (06) :585S-590S

[14] Cancer-associated transforming growth factor β type II receptor gene mutant causes activation of bone morphogenic protein-Smads and invasive phenotype [J].

Bharathy, Savita ;

Xie, Wen ;

Yingling, Jonathan M. ;

Reiss, Michael .

CANCER RESEARCH, 2008, 68 (06) :1656-1666

[15] Stromal fibroblasts in cancer initiation and progression [J].

Bhowmick, NA ;

Neilson, EG ;

Moses, HL .

NATURE, 2004, 432 (7015) :332-337

[16] Tumor-stroma interactions [J].

Bhowmick, NA ;

Moses, HL .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2005, 15 (01) :97-101

[17] TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia [J].

Bhowmick, NA ;

Chytil, A ;

Plieth, D ;

Gorska, AE ;

Dumont, N ;

Shappell, S ;

Washington, MK ;

Neilson, EG ;

Moses, HL .

SCIENCE, 2004, 303 (5659) :848-851

[18] Integrin β1 signaling is necessary for transforming growth factor-β activation of p38MAPK and epithelial plasticity [J].

Bhowmick, NA ;

Zent, R ;

Ghiassi, M ;

McDonnell, M ;

Moses, HL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (50) :46707-46713

[19] Transforming growth factor-β1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism [J].

Bhowmick, NA ;

Ghiassi, M ;

Bakin, A ;

Aakre, M ;

Lundquist, CA ;

Engel, ME ;

Arteaga, CL ;

Moses, HL .

MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (01) :27-36

[20] TGFβ:: the molecular Jekyll and Hyde of cancer [J].

Bierie, Brian ;

Moses, Harold L. .

NATURE REVIEWS CANCER, 2006, 6 (07) :506-520

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