Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
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DOI：
10.1158/0008-5472.can-09-3644
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发表时间：
2010-04-01
期刊：
影响因子：
11.2
通讯作者：
Ostman, Arne
中科院分区：
文献类型：
--
作者：
Saito, Roy-Akira;Micke, Patrick;Ostman, Arne
癌症相关成纤维细胞（CAF）由于其刺激例如肿瘤生长、侵袭、血管生成和转移的能力而作为潜在的癌症药物靶标吸引越来越多的关注。然而，导致CAFs促肿瘤特性的分子机制仍然知之甚少。叉头盒F1（FoxF 1）是刺猬信号传导的间充质靶点，已知在肺发育期间调节间充质-上皮相互作用。对FoxF 1功能获得和丧失的成纤维细胞的研究表明，FoxF 1调节成纤维细胞的收缩性、肝细胞生长因子和成纤维细胞生长因子-2的产生以及它们对肺癌细胞迁移的刺激。还显示成纤维细胞的FoxF 1状态控制成纤维细胞刺激异种移植肿瘤生长的能力。FoxF 1在人肺癌CAFs中表达，并与hedgehog信号通路的激活相关。这些观察结果表明，刺猬依赖性FoxF 1是一个临床相关的肺CAF诱导因子，并支持实验的一般概念，CAF属性可以诱导发育重要的转录因子的激活。Cancer Res; 70（7）; 2644-54. (C)2010年AACR。
Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability to stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing the tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target of hedgehog signaling, known to regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain-and loss-of-function fibroblasts revealed that FoxF1 regulates the contractility of fibroblasts, their production of hepatocyte growth factor and fibroblast growth factor-2, and their stimulation of lung cancer cell migration. FoxF1 status of fibroblasts was also shown to control the ability of fibroblasts to stimulate xenografted tumor growth. FoxF1 was expressed in CAFs of human lung cancer and associated with activation of hedgehog signaling. These observations suggest that hedgehog-dependent FoxF1 is a clinically relevant lung CAF-inducing factor, and support experimentally the general concept that CAF properties can be induced by activation of developmentally important transcription factors. Cancer Res; 70(7); 2644-54. (C) 2010 AACR.