CD44 promotes Kras-dependent lung adenocarcinoma

Oncogene. 2013 Oct 24;32(43):5186-90. doi: 10.1038/onc.2012.542. Epub 2012 Dec 3.


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.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Targeted Therapy
  • Mutation
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Signal Transduction


  • CD44 protein, human
  • Hyaluronan Receptors
  • Mitogen-Activated Protein Kinases
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)