Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Corrigendum Free access | 10.1172/JCI70810

Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer

Sampurna Chatterjee,1 Lukas C. Heukamp,2 Maike Siobal,1 Jakob Schöttle,1 Caroline Wieczorek,1 Martin Peifer,1 Davide Frasca,2 Mirjam Koker,1 Katharina König,2 Lydia Meder,2 Daniel Rauh,3 Reinhard Buettner,2 Jürgen Wolf,4 Rolf A. Brekken,5 Bernd Neumaier,1 Gerhard Christofori,6 Roman K. Thomas,2,7 and Roland T. Ullrich1,4

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Chatterjee, S. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Heukamp, L. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Siobal, M. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Schöttle, J. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Wieczorek, C. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Peifer, M. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Frasca, D. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Koker, M. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by König, K. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Meder, L. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Rauh, D. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Buettner, R. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Wolf, J. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Brekken, R. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Neumaier, B. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Christofori, G. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Thomas, R. in: PubMed | Google Scholar

1Max Planck Institute for Neurological Research, with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany. 2Institute of Pathology, University Hospital Medical School, Cologne, Germany. 3Fakultät Chemie, Chemische Biologie, Technische Universität Dortmund, Dortmund, Germany. 4Department I of Internal Medicine and Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. 5Departments of Surgery and Pharmacology, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 6Institute of Biochemistry and Genetics, Department of Biomedicine, Basel, Switzerland. 7Department of Translational Genomics, University of Cologne, Cologne, Germany.

Find articles by Ullrich, R. in: PubMed | Google Scholar

Published July 1, 2013 - More info

Published in Volume 123, Issue 7 on July 1, 2013
J Clin Invest. 2013;123(7):3183–3183. https://doi.org/10.1172/JCI70810.
© 2013 The American Society for Clinical Investigation
Published July 1, 2013 - Version history
View PDF

Related article:

Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer
Sampurna Chatterjee, … , Roman K. Thomas, Roland T. Ullrich
Sampurna Chatterjee, … , Roman K. Thomas, Roland T. Ullrich
Research Article Oncology

Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer

  • Text
  • PDF
Abstract

The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors and initiate the angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. This disruption was sufficient to prevent tumor growth in vivo. In patients with lung cancer, we found that this VEGF:VEGFR2 feed-forward loop was active, as the level of VEGF/VEGFR2 binding in tumor cells was highly correlated to tumor angiogenesis. We further demonstrated that inhibition of tumor cell VEGFR2 induces feedback activation of the IRS/MAPK signaling cascade. Most strikingly, combined pharmacological inhibition of VEGFR2 (ZD6474) and MEK (PD0325901) in tumor cells resulted in dramatic tumor shrinkage, whereas monotherapy only modestly slowed tumor growth. Thus, a tumor cell-autonomous VEGF:VEGFR2 feed-forward loop provides signal amplification required for the establishment of fully angiogenic tumors in lung cancer. Interrupting this feed-forward loop switches tumor cells from an angiogenic to a proliferative phenotype that sensitizes tumor cells to MAPK inhibition.

Authors

Sampurna Chatterjee, Lukas C. Heukamp, Maike Siobal, Jakob Schöttle, Caroline Wieczorek, Martin Peifer, Davide Frasca, Mirjam Koker, Katharina König, Lydia Meder, Daniel Rauh, Reinhard Buettner, Jürgen Wolf, Rolf A. Brekken, Bernd Neumaier, Gerhard Christofori, Roman K. Thomas, Roland T. Ullrich

×

Original citation: J. Clin. Invest. 2013;123(4):1732–1740. doi:10.1172/JCI65385.

Citation for this corrigendum: J. Clin. Invest. 2013;123(7):3183. doi:10.1172/JCI70810.

The affiliations for Roman K. Thomas were incorrect. The correct affiliations list is above.

The authors regret the error.

Version history
  • Version 1 (July 1, 2013): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts