Latent bone metastasis in breast cancer tied to Src-dependent survival signals

By X. Zhang, Qiongqing Wang, W. Gerald, C. Hudis, Larry Norton, Marcel Smid, John A. Foekens, J. Massagué. Cancer Cell, 2009

677 citations recorded by the source corpus.

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 c-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, c-Src is dispensable for homing to the bones or lungs critical for the survival and outgrowth of these cells in the bone marrow. c-Src mediates AKT regulation and cancer cell survival responses to CXCL12 and TRAIL, factors which are distinctively expressed in the bone metastasis microenvironment. Breast cancer cells that lodge in the bone marrow succumb in this environment when deprived of c-Src activity.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/378be3808b421b434e17be67bbc14595d2c75d9d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. X. Zhang
2. Thordur Oskarsson
3. J. Massagué
4. D. Haber
5. R. Weinberg
6. A. Moustakas
7. C. Heldin
8. E. Batlle

In Oncology

1. X. Zhang
2. Thordur Oskarsson
3. J. Massagué
4. Swarnali Acharyya
5. R. Weinberg
6. Jing Yang
7. J. Tsai
8. D. Pattabiraman

Citations in the corpus

• EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS (2017, neutral): “In one well-studied case, breast cancer cells that have lodged in the bone marrow and possess high SRC activity and expression of CXCR4 are able to activate pro-survival pathways in response to bone-derived CXCL12 (Zhang et al., 2009).”
• A CXCL1 paracrine network links cancer chemoresistance and metastasis (2012, neutral): “Microarray data from human tumor data sets were processed as described (Zhang et al., 2009).”
• Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs (2011, background): “) and 67 metastatic breast tumors from different distant sites (GSE14020; ref”
• Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis (2014, background): “…tropism studies in the mouse have identified subsets of genes involved in breast cancer metastases to lung (e.g., Epiregulin, CXCL1, SPARC, andMMP2) (Minn et al., 2005), brain (e.g., COX2, HBEGF, and ST6GALNAC5) (Bos et al., 2009), and bone (mainly driven by Src activation) (Zhang et al., 2009).”
• Cancer to bone: a fatal attraction (2011, neutral): “Molecular characterization of disseminated breast cancer cells in the bone marrow has revealed the specific expression of a subgroup of transcripts, including the metastasis regulator TWIST1 , and SRC activatio”