Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis

Allison N. Lau, Stephen J. Curtis, Christine M. Fillmore, Samuel P. Rowbotham, Morvarid Mohseni, Darcy E. Wagner, Alexander M. Beede, Daniel T. Montoro, Kerstin W. Sinkevicius, Zandra E. Walton, Juliana Barrios, Daniel J. Weiss, Fernando D. Camargo, Kwok Kin Wong, Carla F. Kim

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24-dependent and Yap/Taz-dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease.

Original languageEnglish
Pages (from-to)468-481
Number of pages14
JournalEMBO Journal
Volume33
Issue number5
DOIs
StatePublished - Mar 3 2014

Keywords

  • CD24
  • Taz
  • lung cancer
  • metastasis
  • tumor propagating cells

ASJC Scopus subject areas

  • Neuroscience (all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)

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