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Microenvironment and Immunology

Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer

Roy-Akira Saito, Patrick Micke, Janna Paulsson, Martin Augsten, Cristina Peña, Per Jönsson, Johan Botling, Karolina Edlund, Leif Johansson, Peter Carlsson, Karin Jirström, Kohei Miyazono and Arne Östman
Roy-Akira Saito
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Patrick Micke
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Janna Paulsson
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Martin Augsten
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Cristina Peña
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Per Jönsson
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Johan Botling
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Karolina Edlund
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Leif Johansson
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Karin Jirström
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Kohei Miyazono
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Arne Östman
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DOI: 10.1158/0008-5472.CAN-09-3644
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Abstract

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

Keywords
  • FoxF1
  • CAF
  • HGF
  • FGF-2
  • lung cancer

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received October 2, 2009.
  • Revision received December 30, 2009.
  • Accepted January 11, 2010.
  • ©2010 American Association for Cancer Research.
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Published OnlineFirst March 16, 2010
doi: 10.1158/0008-5472.CAN-09-3644

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Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
Roy-Akira Saito, Patrick Micke, Janna Paulsson, Martin Augsten, Cristina Peña, Per Jönsson, Johan Botling, Karolina Edlund, Leif Johansson, Peter Carlsson, Karin Jirström, Kohei Miyazono and Arne Östman
Cancer Res March 16 2010 DOI: 10.1158/0008-5472.CAN-09-3644

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Forkhead Box F1 Regulates Tumor-Promoting Properties of Cancer-Associated Fibroblasts in Lung Cancer
Roy-Akira Saito, Patrick Micke, Janna Paulsson, Martin Augsten, Cristina Peña, Per Jönsson, Johan Botling, Karolina Edlund, Leif Johansson, Peter Carlsson, Karin Jirström, Kohei Miyazono and Arne Östman
Cancer Res March 16 2010 DOI: 10.1158/0008-5472.CAN-09-3644
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Cancer Research Online ISSN: 1538-7445
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Journal of Cancer Research ISSN: 0099-7013
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