Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
2010; American Association for Cancer Research; Volume: 70; Issue: 7 Linguagem: Inglês
10.1158/0008-5472.can-09-3644
ISSN1538-7445
AutoresRoy-Akira Saito, Patrick Micke, Janna Paulsson, Martin Augsten, Cristina Peña, Per Jönsson, Johan Botling, Karolina Edlund, Leif Johansson, Peter Carlsson, Karin Jirström, Kohei Miyazono, Arne Östman,
Tópico(s)FOXO transcription factor regulation
ResumoCancer-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.
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