WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis Journal Article
| Authors: | Nguyen, D. X.; Chiang, A. C.; Zhang, X. H. F.; Kim, J. Y.; Kris, M. G.; Ladanyi, M.; Gerald, W. L.; Massague, J. |
| Article Title: | WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis |
| Abstract: | Metastasis from lung adenocarcinoma can occur swiftly to multiple organs within months of diagnosis. The mechanisms that confer this rapid metastatic capacity to lung tumors are unknown. Activation of the canonical WNT/TCF pathway is identified here as a determinant of metastasis to brain and bone during lung adenocarcinoma progression. Gene expression signatures denoting WNT/TCF activation are associated with relapse to multiple organs in primary lung adenocarcinoma. Metastatic subpopulations isolated from independent lymph node-derived lung adenocarcinoma cell lines harbor a hyperactive WNT/TCF pathway. Reduction of TCF activity in these cells attenuates their ability to form brain and bone metastases in mice, independently of effects on tumor growth in the lungs. The WNT/TCF target genes HOXB9 and LEF1 are identified as mediators of chemotactic invasion and colony outgrowth. Thus, a distinct WNT/TCF signaling program through LEF1 and HOXB9 enhances the competence of lung adenocarcinoma cells to colonize the bones and the brain. For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; unclassified drug; human cell; cancer growth; nonhuman; bone metastasis; disease free survival; adenocarcinoma; mouse; animals; mice; mus; gene expression profiling; signaling; lung neoplasms; animal experiment; animal model; genetic association; homeodomain proteins; mice, scid; cell line, tumor; distant metastasis; cancer invasion; lung adenocarcinoma; mice, nude; brain metastasis; neoplasm metastasis; transplantation, heterologous; cancer relapse; neoplasm transplantation; tumor growth; mice, inbred nod; wnt proteins; wnt protein; humdisease; t cell factor protein; hox protein; hoxb9 protein; lymphoid enhancer factor 1; lymphoid enhancer-binding factor 1; tcf transcription factors |
| Journal Title: | Cell |
| Volume: | 138 |
| Issue: | 1 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2009-07-10 |
| Start Page: | 51 |
| End Page: | 62 |
| Language: | English |
| DOI: | 10.1016/j.cell.2009.04.030 |
| PUBMED: | 19576624 |
| PROVIDER: | scopus |
| PMCID: | PMC2742946 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 20" - "Export Date: 30 November 2010" - "CODEN: CELLB" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work