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CD44 promotes Kras-dependent lung adenocarcinoma

Oncogene volume 32, pages 5186–5190 (2013)Cite this article

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Abstract

Kras-induced non-small-cell lung adenocarcinoma is the major subtype of lung cancers and is associated with poor prognosis. Using a lung cancer mouse model that expresses a cre-mediated KrasG12D mutant, we identified a critical role for the cell surface molecule CD44 in mediating cell proliferation downstream of oncogenic Kras signaling. The deletion of CD44 attenuates lung adenocarcinoma formation and prolongs the survival of these mice. Mechanistically, CD44 is required for the activation of Kras-mediated signaling through the mitogen-activated protein kinase (MAPK) pathway and thus promotes tumor cell proliferation. Together, these results reveal an unrecognized role for CD44 in oncogenic Kras-induced lung adenocarcinoma and suggest that targeting CD44 could be an effective strategy for halting Kras-dependent carcinomas.

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Acknowledgements

We thank Dr Tyler Jacks for providing the LSL-K-RasG12D mouse strain and Kim Mercer for technical assistance. We also thank members in the Cheng laboratory for discussions and suggestions.

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Author notes

  1. P Zhao and M S Damerow: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    P Zhao, M S Damerow, A H Liu & C Cheng

  2. Sextant Therapeutics Inc, Cambridge, MA, USA

    P Stern

  3. Department of Pediatrics, Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA

    A Sweet-Cordero

  4. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    K Siziopikou

  5. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA

    J R Neilson

  6. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    P A Sharp

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  1. P Zhao
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  8. P A Sharp
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  9. C Cheng
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Correspondence to C Cheng.

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Supplementary Information accompanies the paper on the Oncogene website

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Zhao, P., Damerow, M., Stern, P. et al. CD44 promotes Kras-dependent lung adenocarcinoma. Oncogene 32, 5186–5190 (2013). https://doi.org/10.1038/onc.2012.542

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  • DOI: https://doi.org/10.1038/onc.2012.542

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