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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.