Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/15148
Title: SOX11 promotes invasive growth and ductal carcinoma in situ progression
Authors: Oliemuller, E
Kogata, N
Bland, P
Kriplani, D
Daley, F
Haider, S
Shah, V
Sawyer, EJ
Howard, BA
Keywords: SOX11;DCIS;Embryonic mammary marker;Mammary progenitor/stem cells;Invasion;ALDH1A1
Issue Date: 2017
Publisher: Wiley Open Access
Citation: The Journal of Pathology, (2017)
Abstract: Here, we show that SOX11, an embryonic mammary marker that is normally silent in postnatal breast cells, is expressed in many oestrogen receptor-negative preinvasive ductal carcinoma in situ (DCIS) lesions. Mature mammary epithelial cells engineered to express SOX11 showed alterations in progenitor cell populations, including an expanded basal-like population with increased aldehyde dehydrogenase (ALDH) activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 showed increased ALDH activity, which is 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 led to increased invasive growth both in vitro and when they were injected intraductally in a mouse model of DCIS that recapitulates human disease. Invasive lesions formed sooner and tumour growth was augmented in vivo, suggesting that 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 that SOX11 is a potential biomarker for DCIS lesions containing cells harbouring distinct biological features that are likely to progress to invasive breast cancer.
URI: http://bura.brunel.ac.uk/handle/2438/15148
DOI: http://dx.doi.org/10.1002/path.4939
ISSN: 0022-3417
Appears in Collections:Dept of Life Sciences Research Papers

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