间质细胞
癌症研究
转移
结直肠癌
串扰
转化生长因子
肿瘤微环境
医学
癌症
生物
癌细胞
内科学
肿瘤细胞
光学
物理
作者
Alexandre Calon,Elisa Espinet,Sergio Palomo,Daniele V. F. Tauriello,Mar Iglesias,María Virtudes Céspedes,Marta Sevillano,Cristina Nadal,Peter Jung,Xiang H.-F. Zhang,Daniel Byrom,Antoni Riéra,David Rossell,Ramón Mangues,Joan Massagué,Elena Sancho,Eduard Batlle
出处
期刊:Cancer Cell
[Elsevier]
日期:2012-11-01
卷期号:22 (5): 571-584
被引量:926
标识
DOI:10.1016/j.ccr.2012.08.013
摘要
A large proportion of colorectal cancers (CRCs) display mutational inactivation of the TGF-β pathway, yet, paradoxically, they are characterized by elevated TGF-β production. Here, we unveil a prometastatic program induced by TGF-β in the microenvironment that associates with a high risk of CRC relapse upon treatment. The activity of TGF-β on stromal cells increases the efficiency of organ colonization by CRC cells, whereas mice treated with a pharmacological inhibitor of TGFBR1 are resilient to metastasis formation. Secretion of IL11 by TGF-β-stimulated cancer-associated fibroblasts (CAFs) triggers GP130/STAT3 signaling in tumor cells. This crosstalk confers a survival advantage to metastatic cells. The dependency on the TGF-β stromal program for metastasis initiation could be exploited to improve the diagnosis and treatment of CRC.
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