Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer

被引：479

作者：

Pardali, Katenna ^{[1
]}

Moustakas, Aristidis ^{[1
]}

机构：

[1] Uppsala Univ, Ludwig Inst Canc Res, SE-75124 Uppsala, Sweden

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2007年 / 1775卷 / 01期

关键词：

cancer; epithelial-mesenchymal transition; metastasis; Smad; TGF-beta; tumor suppressor;

D O I：

10.1016/j.bbcan.2006.06.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transforming growth factor-beta (TGF-beta) is a secreted polypeptide that signals via receptor serine/threonine kinases and intracellular Smad effectors. TGF-beta inhibits proliferation and induces apoptosis in various cell types, and accumulation of loss-of-function mutations in the TGF-beta receptor or Smad genes classify the pathway as a tumor suppressor in humans. In addition, various oncogenic pathways directly inactivate the TGF-beta receptor-Smad pathway, thus favoring tumor growth. On the other hand, all human tumors overproduce TGF-beta whose autocrine and paracrine actions promote tumor cell invasiveness and metastasis. Accordingly, TGF-beta induces epithelial-mesenchymal transition, a differentiation switch that is required for transitory invasiveness of carcinoma cells. Tumor-derived TGF-beta acting on stromal fibroblasts remodels the tumor matrix and induces expression of mitogenic signals towards the carcinoma cells, and upon acting on endothelial cells and pericytes, TGF-beta regulates angiogenesis. Finally, TGF-beta suppresses proliferation and differentiation of lymphocytes including cytolytic T cells, natural killer cells and macrophages, thus preventing immune surveillance of the developing tumor. Current clinical approaches aim at establishing novel cancer drugs whose mechanisms target the TGF-beta pathway. In conclusion, TGF-beta signaling is intimately implicated in tumor development and contributes to all cardinal features of tumor cell biology. (c) 2006 Elsevier B.V. All rights reserved.

引用

页码：21 / 62

页数：42

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