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

Lau, Allison N.; Curtis, Stephen J.; Fillmore, Christine M.; Rowbotham, Samuel P.; Mohseni, Morvarid; Wagner, Darcy E. LU ; Beede, Alexander M.; Montoro, Daniel T.; Sinkevicius, Kerstin W. and Walton, Zandra E., et al. (2014) In EMBO Journal 33(5). p.468-481
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
CD24, lung cancer, metastasis, Taz, tumor propagating cells
in
EMBO Journal
volume
33
issue
5
pages
468 - 481
publisher
Oxford University Press
external identifiers
  • scopus:84898640056
ISSN
0261-4189
DOI
10.1002/embj.201386082
language
English
LU publication?
no
id
7b74b93f-5fba-41b5-b114-507702cfe2f1
date added to LUP
2017-08-15 15:15:34
date last changed
2017-11-12 04:34:27
@article{7b74b93f-5fba-41b5-b114-507702cfe2f1,
  abstract     = {<p>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.</p>},
  author       = {Lau, Allison N. and Curtis, Stephen J. and Fillmore, Christine M. and Rowbotham, Samuel P. and Mohseni, Morvarid and Wagner, Darcy E. and Beede, Alexander M. and Montoro, Daniel T. and Sinkevicius, Kerstin W. and Walton, Zandra E. and Barrios, Juliana and Weiss, Daniel J. and Camargo, Fernando D. and Wong, Kwok Kin and Kim, Carla F.},
  issn         = {0261-4189},
  keyword      = {CD24,lung cancer,metastasis,Taz,tumor propagating cells},
  language     = {eng},
  month        = {03},
  number       = {5},
  pages        = {468--481},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis},
  url          = {http://dx.doi.org/10.1002/embj.201386082},
  volume       = {33},
  year         = {2014},
}