SOX11 promotes invasive growth and DCIS progression.

Abstract

Here, we show that SOX11, an embryonic mammary marker, normally silent in postnatal breast cells, is expressed in many ER-negative (ER-) preinvasive DCIS lesions. Mature mammary epithelial cells engineered to express SOX11 displayed alterations in progenitor cell populations, including an expanded basal-like population with increased ALDH activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 displayed increased ALDH activity, a feature of cancer stem cells. The CD44+/CD24-/ALDH+ cell population was increased in DCIS.com cells that expressed SOX11. Upregulating SOX11 expression in DCIS.com cells lead to increased invasive growth both in vitro and when injected intraductally in a mouse model of DCIS that recapitulates human disease. Invasive lesions formed sooner and tumour growth was augmented in vivo, suggesting SOX11 contributes to the progression of DCIS to invasive breast cancer. We identified potential downstream effectors of SOX11 during both microinvasive and invasive tumour growth stages, including several with established links to regulation of progenitor cell function and prenatal developmental growth. Our findings suggest SOX11 is a potential biomarker for DCIS lesions containing cells harbouring distinct biological features, which are likely to progress to invasive breast cancer.