Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis
(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.
(Less)
- author
- publishing date
- 2014-03-03
- 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
- 2022-03-17 00:17:34
@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}}, keywords = {{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}}, doi = {{10.1002/embj.201386082}}, volume = {{33}}, year = {{2014}}, }