2014/01/14

Sox2 promotes tamoxifen resistance in breast cancer cells

A study by the group of Maria Vivanco, in collaboration with the group of Robert Kypta (also at CIC bioGUNE), Dr Zabalza (Hospital of Galdakao) and Dr López-Ruiz (PreteImagen) has been published this week in the prestigious journal EMBO Molecular Medicine.

The work addresses the development of resistance to therapy, which continues to be a serious clinical problem in breast cancer management. Here it is shown that cancer stem cells play a role in the development of resistance to tamoxifen therapy. Tumours that are resistant to the effects of tamoxifen are enriched for stem/progenitor cells and express high levels of the stem cell marker Sox2. Silencing of the Sox2 gene in breast cancer cells was found to reduce the population of cancer stem cells and to restore tamoxifen sensitivity. The development of resistance to tamoxifen involves Sox2-dependent activation of the Wnt signalling pathway.

This study indicates the relevance of Sox2 in the development of resistance to tamoxifen and suggests Sox2 as a potential biomarker for tamoxifen resistance. Furthermore, it provides a link between Sox2 expression, cancer stem cells and autocrine Wnt signalling in tamoxifen-resistant tumours. Combining hormone therapy with Wnt or Sox2 inhibitors might therefore provide a novel strategy to treat breast cancer and prevent recurrence.

The article, which is highlighted on the cover page of the current issue of the journal, has been selected for Faculty1000Prime and recommended as being of special significance in its field.

Piva M, Domenici G, Iriondo O, Rábano M, Simoes B, Comaills V, Barredo I, López-Ruiz JA, Zabalza I, Kpyta R and Vivanco MdM.

Sox2 promotes tamoxifen resistance in breast cancer cells.
EMBO Mol Med (2014) 6(1) 66-79. doi: 10.1002/emmm.201303411