SOX11 promotes invasive growth and ductal carcinoma in situ progression

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. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non‐epithelial tumours

“…A small subset of breast carcinomas, not otherwise specified (NOS) (six of 36, 17%), demonstrated strong or intermediate nuclear expression of SOX11 (Figure E,F). These SOX11‐positive cases showed ER − /PR − /HER2 +/− immunophenotypes, which is consistent with the previous report that SOX11 is highly expressed in basal‐like and HER2 + breast cancers . For adenocarcinoma of the female genital tract, weak SOX11 expression was (sporadically, with <20% of tumour cells for each case) detected in three of 19 high‐grade serous carcinomas (Figure G,H), but not in low‐grade serous carcinomas ( n = 21) or other types of genital adenocarcinomas, including 30 mucinous carcinomas, 34 endometrioid carcinomas and 11 clear‐cell carcinomas.…”

“…These SOX11-positive cases showed ER À /PR À /HER2 +/À immunophenotypes, which is consistent with the previous report that SOX11 is highly expressed in basal-like and HER2 + breast cancers. 21 For adenocarcinoma of the female genital tract, weak SOX11 expression was (sporadically, with <20% of tumour cells for each case) detected in three of 19 high-grade serous carcinomas ( Figure 2G,H pulmonary adenocarcinomas and two of 57 of large cell carcinomas showed intermediate nuclear staining of SOX11. One SOX11 + pulmonary adenocarcinoma demonstrated neuroendocrine differentiation by other neuroendocrine markers, such as synaptophysin, CGA and CD56, and the two SOX11 + large cell carcinomas seemed to show neuroendocrine morphology.…”

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

“…It has been reported that lncRNA DLX6-AS1 was up-regulated in lung adenocarcinoma (LAC) tissues compared to paired adjacent normal lung tissues and high DLX6-AS1 expression levels were significantly associated with both histological differentiation and TNM stage [41]. Recent researches have demonstrated that FSCN1, SOX11 and PSAT1 were associated with poor clinical outcome in breast cancer [42][43][44]. Our results are consistent with these reports.…”

A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts

“…The MIND model was utilised in our studies as previously described [35, 54]. Briefly, a suspension of 5 × 10 4 MCF10DCIS.com-Luc cells was injected intraductally into mammary gland ducts of 6-10 week-old SCID-beige female mouse (n=7-8).…”