Latent bone metastasis in breast cancer tied to Src-dependent survival signals Journal Article
| Authors: | Zhang, X. H. F.; Wang, Q.; Gerald, W.; Hudis, C. A.; Norton, L.; Smid, M.; Foekens, J. A.; Massague, J. |
| Article Title: | Latent bone metastasis in breast cancer tied to Src-dependent survival signals |
| Abstract: | Metastasis may arise years after removal of a primary tumor. The mechanisms allowing latent disseminated cancer cells to survive are unknown. We report that a gene expression signature of Src activation is associated with late-onset bone metastasis in breast cancer. This link is independent of hormone receptor status or breast cancer subtype. In breast cancer cells, Src is dispensable for homing to the bones or lungs but is critical for the survival and outgrowth of these cells in the bone marrow. Src mediates AKT regulation and cancer cell survival responses to CXCL12 and TNF-related apoptosis-inducing ligand (TRAIL), factors that are distinctively expressed in the bone metastasis microenvironment. Breast cancer cells that lodge in the bone marrow succumb in this environment when deprived of Src activity. © 2009 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; bone neoplasms; disease-free survival; human cell; nonhuman; bone metastasis; mouse; cell survival; breast cancer; gene expression; bone marrow; animal experiment; animal model; breast neoplasms; gene expression regulation, neoplastic; nucleotide sequence; cancer cell; tumor necrosis factor related apoptosis inducing ligand; proto-oncogene proteins c-akt; bone; lung; neoplasm metastasis; cellcycle; microenvironment; cancer classification; steroid receptor coactivator 1; cell homing; stromal cell derived factor 1; chemokine cxcl12; proto-oncogene proteins pp60(c-src); receptors, cxcr4; tnf-related apoptosis-inducing ligand |
| Journal Title: | Cancer Cell |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2009-07-07 |
| Start Page: | 67 |
| End Page: | 78 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2009.05.017 |
| PUBMED: | 19573813 |
| PROVIDER: | scopus |
| PMCID: | PMC2749247 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 29" - "Export Date: 30 November 2010" - "CODEN: CCAEC" - "Source: Scopus" |
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