Latent Bone Metastasis in Breast Cancer Tied to Src-Dependent Survival Signals

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 hormo...

Full description

Saved in:
Bibliographic Details
Published in:Cancer cell 2009-07, Vol.16 (1), p.67-78
Main Authors: Zhang, Xiang H.-F., Wang, Qiongqing, Gerald, William, Hudis, Clifford A., Norton, Larry, Smid, Marcel, Foekens, John A., Massagué, Joan
Format: Article
Language:English
Subjects:
Bone Marrow - pathology
Bone Marrow - physiopathology
Bone Neoplasms - enzymology
Bone Neoplasms - genetics
Bone Neoplasms - pathology
Bone Neoplasms - secondary
Breast Neoplasms - embryology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Survival
CELLCYCLE
Chemokine CXCL12 - metabolism
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Lung - pathology
Neoplasm Metastasis - pathology
Proto-Oncogene Proteins c-akt - metabolism
Proto-Oncogene Proteins pp60(c-src) - genetics
Proto-Oncogene Proteins pp60(c-src) - metabolism
Receptors, CXCR4 - metabolism
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2009.05.017