SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells

eLife

Iskander Aurrekoetxea-Rodríguez¹  Maria dM Vivanco¹  Gareth Muirhead²  Siu Man Tsang²  Syed Haider²  Erik Oliemuller²  Farzana Noor²  Richard Newman²  Beatrice A Howard²  Shane Foo³ 

[1] CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain;The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom;Translational Immunotherapy Team, Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom;

关键词: SOX11;    DCIS;    breast cancer;    MEX3A;   

DOI  :  10.7554/eLife.58374

来源: DOAJ

【 摘 要 】

SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. Here, we show that SOX11 confers distinct features to ER-negative DCIS.com breast cancer cells, leading to populations enriched with highly plastic hybrid epithelial/mesenchymal cells, which display invasive features and alterations in metastatic tropism when xenografted into mice. We found that SOX11+DCIS tumour cells metastasize to brain and bone at greater frequency and to lungs at lower frequency compared to cells with lower SOX11 levels. High levels of SOX11 leads to the expression of markers associated with mesenchymal state and embryonic cellular phenotypes. Our results suggest that SOX11 may be a potential biomarker for breast tumours with elevated risk of developing metastases and may require more aggressive therapies.

【 授权许可】

Unknown