A multigenic program mediating breast cancer metastasis to bone

Yibin Kang, Peter M. Siegel, Weiping Shu, Maria Drobnjak, Sanna M. Kakonen, Carlos Cordón-Cardo, Theresa A. Guise, Joan Massagué

Research output: Contribution to journalArticlepeer-review

2121 Scopus citations


We investigated the molecular basis for osteolytic bone metastasis by selecting human breast cancer cell line subpopulations with elevated metastatic activity and functionally validating genes that are overexpressed in these cells. These genes act cooperatively to cause osteolytic metastasis, and most of them encode secreted and cell surface proteins. Two of these genes, interleukin-11 and CTGF, encode osteolytic and angiogenic factors whose expression is further increased by the prometastatic cytokine TGFβ. Overexpression of this bone metastasis gene set is superimposed on a poor-prognosis gene expression signature already present in the parental breast cancer population, suggesting that metastasis requires a set of functions beyond those underlying the emergence of the primary tumor.

Original languageEnglish (US)
Pages (from-to)537-549
Number of pages13
JournalCancer Cell
Issue number6
StatePublished - Jun 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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