Journal
CANCER LETTERS
Volume 380, Issue 1, Pages 78-86Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.06.007
Keywords
RUNX2; Integrin alpha 5; Bone metastasis; Breast cancer
Categories
Funding
- National Natural Science Foundation of China [30872518, 81201647, 81272357, 81472680]
- Major Program of Applied Basic Research Projects of Tianjin [09JCZDJC19800, 13JCZDJC30100]
- Specialized Research Fund for the Doctoral Program of Higher Education of the Ministry of Education of China [20121202120011]
- Science Technology Development Project of Colleges and Universities in Tianjin [20090134]
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Runt-related transcription factor 2 (RUNX2) is regarded as an important contributor to breast cancer bone metastasis. However, previous studies did not provide direct clinical evidence for a role of RUNX2 in bone specific metastasis in breast cancer, and the mechanism of RUNX2 in cancer cell recruitment and adhesion to the bone remains unclear. In this study, we showed that RUNX2 expression is positively correlated with the risk of bone-specific metastasis in lymph node-negative breast cancer patients. Then, we identified ITGA5 as a transcriptional target of RUNX2 from multiple candidate genes encoding adhesion molecules or chemokine receptors. We further provided experimental and clinical evidence that RUNX2, in an integrin alpha 5-dependent manner, promotes the attraction and adhesion of breast cancer cells to the bone and confers cancer cell survival and bone colonization advantages. Overall, our findings clarify an adhesion dependent mechanism of RUNX2 for the osteotropism and bone colonization of breast cancer cells and implicate RUNX2 and integrin alpha 5 as potential molecular markers for the prediction of bone metastasis and therapeutic targets for the treatment of breast cancer bone metastasis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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