An oncogene expressed by a minority of breast cancer cells drives metastasis
Studies led by Ludwig Stanford’s Michael Clarke have shown that a small population of cancer cells that exist in an immature state in breast tumors are primarily responsible for metastatic outgrowths. In a November paper in Science Advances, Michael and his colleagues reported that among these cells, those that express the oncogene LMO2 and display angiogenic features appear to be especially prone to initiating metastasis. Cells derived from this lineage, they show, integrate into the tumor vasculature in mouse models and have a higher propensity to metastasize. Suppressing LMO2 expression in human breast tumor cells reduced lung metastases in mice by compromising their ability to squeeze into blood vessels. This led to a reduction in the number of circulating cancer cells in the mice. The researchers also showed that higher expression of the oncogene in breast basal cells predicts poor distant metastasis-free survival in patients. They found that Lmo2 exerts its effects through regulation of the STAT3 signaling pathway, and that it is required for STAT3 activation by tumor necrosis factor-α and interleukin-6. They suggest that the STAT3-LMO2 signaling axis could be a key target for breast cancer therapy.