Authors' Affiliations: Department of Oncology−Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden; Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden; Departments of Cardiothoracic Surgery and Pathology, Lund University Hospital, Lund, Sweden; Department of Cell and Molecular Biology, University of Gothenburg, Lundberg Laboratory, Gothenburg, Sweden; and Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
Cancer Res. 2010 Mar 16.
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.
PMID: 20233876 [PubMed − as supplied by publisher] Source: National Library of Medicine.
