Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH Journal Article
| Authors: | Urosevic, J.; Garcia-Albéniz, X.; Planet, E.; Real, S.; Céspedes, M. V.; Guiu, M.; Fernandez, E.; Bellmunt, A.; Gawrzak, S.; Pavlovic, M.; Mangues, R.; Dolado, I.; Barriga, F. M.; Nadal, C.; Kemeny, N.; Batlle, E.; Nebreda, A. R.; Gomis, R. R. |
| Article Title: | Colon cancer cells colonize the lung from established liver metastases through p38 MAPK signalling and PTHLH |
| Abstract: | The mechanisms that allow colon cancer cells to form liver and lung metastases, and whether KRAS mutation influences where and when metastasis occurs, are unknown. We provide clinical and molecular evidence showing that different MAPK signalling pathways are implicated in this process. Whereas ERK2 activation provides colon cancer cells with the ability to seed and colonize the liver, reduced p38 MAPK signalling endows cancer cells with the ability to form lung metastasis from previously established liver lesions. Downregulation of p38 MAPK signalling results in increased expression of the cytokine PTHLH, which contributes to colon cancer cell extravasation to the lung by inducing caspase-independent death in endothelial cells of the lung microvasculature. The concerted acquisition of metastatic traits in the colon cancer cells together with the sequential colonization of liver and lung highlights the importance of metastatic lesions as a platform for further dissemination. © 2014 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; human cell; nonhuman; animal cell; mouse; animal tissue; cell death; mitogen activated protein kinase p38; protein protein interaction; animal experiment; animal model; enzyme activation; caspase; endothelium cell; liver metastasis; lung metastasis; cytokine; enzyme regulation; colon cancer; cancer cell; mitogen activated protein kinase 1; cellular distribution; down regulation; molecular biology; microvasculature; cell activity; human; female; priority journal; article; parathyroid hormone like hormone; lung endothelium |
| Journal Title: | Nature Cell Biology |
| Volume: | 16 |
| Issue: | 7 |
| ISSN: | 1465-7392 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2014-07-01 |
| Start Page: | 685 |
| End Page: | 694 |
| Language: | English |
| DOI: | 10.1038/ncb2977 |
| PROVIDER: | scopus |
| PUBMED: | 24880666 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- CODEN: NCBIF -- Source: Scopus |
