Research ArticleCancer

ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling

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Science Signaling  02 Feb 2016:
Vol. 9, Issue 413, pp. ra12
DOI: 10.1126/scisignal.aad3210

Metastatic breast tumors break down bone

Most breast cancer cells activate the breakdown of bone to promote metastases. Wang et al. found that the ABL kinase isoforms ABL1 and ABL2 enhanced the ability of breast cancer cells to invade and break down bone in mice. In breast cancer cells, the ABL kinases activated the transcriptional coactivator TAZ and the transcription factor STAT5, which triggered the transcription of genes encoding factors that activate osteoclasts (cells that break down bone) and those that enhance the survival of breast cancer cells in the bone microenvironment. An ABL-specific inhibitor decreased bone metastasis in mice, thus suggesting that blocking ABL kinase activity could prevent breast cancer cells from promoting bone metastasis.

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