Sox9 regulates cell state and activity of embryonic mouse mammary progenitor cells

Kogata, Naoko; Bland, Philip; Tsang, Mandy; Oliemuller, Erik; Lowe, Anne; Howard, Beatrice A.

doi:10.1038/s42003-018-0215-3

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…Stem cells and progenitors may serve as a cell of origin for breast cancers. Many SOX (SRY-related HMG-box) transcription factors are expressed in the postnatal breast and some have been shown to control normal and/or CSCs ( Domenici et al, 2019 ; Kogata et al, 2018 ; Mehta et al, 2019 ). SOX11 is a unique transcription factor, since it does not appear to be expressed in normal mammary epithelial cells after birth in either mouse or human and therefore is well-poised to reactivate developmental pathways when expressed in breast cancers ( Oliemuller et al, 2017 ; Tsang et al, 2020 ; Wansbury et al, 2011 ; Zvelebil et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

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

Oliemuller

Newman

Tsang

et al. 2020

eLife

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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.

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Section: Discussionmentioning

confidence: 99%

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

Oliemuller

Newman

Tsang

et al. 2020

eLife

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“…S1A " type="url"/> ). eMPC lines were described in our previous study ( Kogata et al, 2018 ). eMPC lines eG2E5 and eG3A8 are more stem cell-like based on gene expression and cluster analysis, and express higher levels of Sox11 than eG2 ( …”

Section: Resultsmentioning

confidence: 99%

Sox11 regulates mammary tumour-initiating and metastatic capacity in Brca1-deficient mouse mammary tumour cells

Tsang

Kim

Oliemuller

et al. 2021

Disease Models &Amp; Mechanisms

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Little is known about the role of Sox11 in the regulation of mammary progenitor cells. Sox11 is expressed by mammary bud epithelial cells during embryonic mammary gland development and is not detected in mammary epithelial cells after birth. As Sox11 is an oncofetal gene, we investigated the effects of reducing Sox11 levels in embryonic mammary progenitor cells and found that Sox11 regulates proliferative state, stem cell activity and lineage marker expression. We also investigated the effect of reducing Sox11 levels in two transplantable Brca1-deficient oestrogen receptor-negative mouse mammary tumour cell lines, to assess whether Sox11 regulates similar functions in tumour progenitor cells. When Sox11 levels were reduced in one Brca1-deficient mammary tumour cell line that expressed both epithelial and mesenchymal markers, similar effects on proliferation, stem cell activity and expression of lineage markers to those seen in the embryonic mammary progenitor cells were observed. Orthotopic grafting of mammary tumour cells with reduced Sox11 levels led to alterations in tumour-initiating capacity, latency, expression of lineage markers and metastatic burden. Our results support a model in which tumours expressing higher levels of Sox11 have more stem and tumour-initiating cells, and are less proliferative, whereas tumours expressing lower levels of Sox11 become more proliferative and capable of morphogenetic/metastatic growth, similar to what occurs during embryonic mammary developmental progression.

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“…Similar to Sox10, the closely related Sox9 has also been implicated in mammary gland development, maintenance of the mammary stem cell state and breast cancer 23,35,36 . Co-expression of the two closely related, structurally highly homologous Sox proteins is not uncommon 19 .…”

Section: Discussionmentioning

confidence: 99%

The transcription factor Sox10 is an essential determinant of branching morphogenesis and involution in the mouse mammary gland

Mertelmeyer

Weider

Baroti

et al. 2020

Sci Rep

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The high mobility group-domain containing transcription factor Sox10 is an essential regulator of developmental processes and homeostasis in the neural crest, several neural crest-derived lineages and myelinating glia. Recent studies have also implicated Sox10 as an important factor in mammary stem and precursor cells. Here we employ a series of mouse mutants with constitutive and conditional Sox10 deficiencies to show that Sox10 has multiple functions in the developing mammary gland. While there is no indication for a requirement of Sox10 in the specification of the mammary placode or descending mammary bud, it is essential for both the prenatal hormone-independent as well as the pubertal hormone-dependent branching of the mammary epithelium and for proper alveologenesis during pregnancy. It furthermore acts in a dosage-dependent manner. Sox10 also plays a role during the involution process at the end of the lactation period. Whereas its effect on epithelial branching and alveologenesis are likely causally related to its function in mammary stem and precursor cells, this is not the case for its function during involution where Sox10 seems to work at least in part through regulation of the miR-424(322)/503 cluster.

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Sox9 regulates cell state and activity of embryonic mouse mammary progenitor cells

Cited by 14 publications

References 49 publications

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

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

Sox11 regulates mammary tumour-initiating and metastatic capacity in Brca1-deficient mouse mammary tumour cells

The transcription factor Sox10 is an essential determinant of branching morphogenesis and involution in the mouse mammary gland

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