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RETRACTED ARTICLE: HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs

Oncogene volume 31, pages 1757–1770 (2012)Cite this article

This article was retracted on 23 May 2023

A Correction to this article was published on 15 January 2021

This article has been updated

Abstract

Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC–EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs.

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Acknowledgements

We are grateful to Karen Padgett of Novus Biologicals for generous gifts of antibodies against HIF-1α, HIF-2α and L1CAM. This work was supported by the Emerald Foundation, the National Institutes of Health (U54-CA143868) and the Johns Hopkins Institute for Cell Engineering. DMG was supported by the Postdoctoral Training Program in Nanotechnology for Cancer Medicine (T32-CA130840). GLS is the C Michael Armstrong Professor at Johns Hopkins University School of Medicine.

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Authors and Affiliations

  1. Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    H Zhang, C C L Wong, H Wei, D M Gilkes, P Chaturvedi, L Schito, J Chen & G L Semenza

  2. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    H Zhang, P Korangath, S Sukumar & G L Semenza

  3. McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C C L Wong, H Wei, D M Gilkes, P Chaturvedi, J Chen & G L Semenza

  4. Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    B Krishnamachary, P T Winnard Jr & V Raman

  5. School of Life Science, The University of Science and Technology of China, Hefei, Anhui, China

    H Zhang

  6. University of Rome ‘La Sapienza’, Rome, Italy

    L Schito

  7. Division of Physiology, The Johns Hopkins University School of Public Health, Baltimore, MD, USA

    L Zhen & W A Mitzner

  8. Departments of Pediatrics, Medicine, Radiation Oncology, and Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    G L Semenza

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Correspondence to G L Semenza.

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Zhang, H., Wong, C., Wei, H. et al. RETRACTED ARTICLE: HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 31, 1757–1770 (2012). https://doi.org/10.1038/onc.2011.365

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