2019/01/18

A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells

New research about the signals controlling normal and cancer stem cells in the human breast has been published in Oncogene (Nature Publishing Group), a leading cancer journal, by the group of Maria Vivanco at CIC bioGUNE, in collaboration with other researchers at CIC bioGUNE and institutions in the Basque Country and the UK.

Breast cancer is a heterogenous disease that remains the cancer with the highest incidence in women and, despite all advances, has the highest mortality for cancer in women in the world. The majority of breast tumours express the estrogen receptor (ER) and are therefore usually treated with hormone therapy, for example, tamoxifen. Unfortunately, tumors develop resistance to treatment and cancer returns, and this is an important clinical problem.

Previous work in the Vivanco laboratory had shown that development of resistance to tamoxifen leads to the enrichment in cells with properties of stem/progenitor cells and that the transcription factor Sox2 plays a key role in this process. In the present work, Sox9 expression, which is directly induced by Sox2, has been found to be required for luminal progenitor cell function in the human breast and for Wnt signalling in tamoxifen resistant breast cancer cells. These findings identify a Sox2-Sox9 network that is crucial for stem/progenitor cell maintenance in the human mammary gland. Importantly, they further highlight the potential importance of Sox proteins as therapeutic targets in breast cancer.