Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression

Liu, Rong; Shi, Peng; Nie, Zhi; Liang, Hongjun; Zhou, Zhongmei; Chen, Wenlin; Chen, Haijun; Dong, Chao; Yang, Runxiang; Liu, Suling; Chen, Ceshi

doi:10.7150/thno.14315

Cited by 109 publications

(118 citation statements)

References 53 publications

(72 reference statements)

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“…We found that Klf5 is required for PyMT oncogeneinduced mammary gland tumor initiation and development, and contributes to tumor cell stemness, indicating an oncogenic function for Klf5 in mammary tumorigenesis. These results are consistent with our previous findings that KLF5 depletion significantly suppresses breast tumor growth in xenograft mouse models [22,23], and that pharmacological inhibition of KLF5 suppresses breast cancer stem cell self-renewal and maintenance [4]. However, PyMT is not a pathologically relevant carcinogen in humans, so that validating the role of Klf5 in breast tumorigenesis by crossing other pathologically relevant breast cancer mouse models with other Klf5 KO mouse models could be useful.…”

Section: R Liu Et Alsupporting

confidence: 92%

“…High expression of KLF5 has been reported to be associated with a worse prognosis and a short survival time in breast cancer patients . Our recent studies found that knockdown of KLF5 suppressed breast tumor growth and breast cancer stem cell maintenance in immune‐knockout mice. We previously reported that KLF5 is induced by progesterone through the progesterone receptor (PR), and Klf5 is highly expressed in mouse mammary glands during pregnancy and lactation .…”

Section: Introductionmentioning

confidence: 84%

“…Slug also mediated these functions of Klf5 in vivo.No conflicts of interest were declared. [22,23] and breast cancer stem cell maintenance [4] in immune-knockout mice. We previously reported that KLF5 is induced by progesterone through the progesterone receptor (PR), and Klf5 is highly expressed in KLF5 and mammary gland development 503 Figure 4.…”

mentioning

confidence: 99%

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Krüpple‐like factor 5 is essential for mammary gland development and tumorigenesis

Liu

Shi

Zhou

et al. 2018

The Journal of Pathology

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Krüpple-like factor 5 (KLF5) is required for the development of the embryo and multiple organs, such as the lung and intestine. KLF5 plays a pro-proliferative and oncogenic role in several carcinomas, including breast cancer. However, its role in normal mammary gland development and oncogenesis has not been elucidated in vivo. In this study, we used mammary gland-specific Klf5 conditional knockout mice derived by mating Klf5-LoxP and MMTV-Cre mice. The genetic ablation of Klf5 suppresses mammary gland ductal elongation and lobuloalveolar formation. Klf5 deficiency inhibits mammary epithelial cell proliferation, survival, and stem cell maintenance. Klf5 promotes mammary stemness, at least partially, by directly promoting the transcription of Slug. Finally, Klf5 depletion suppressed PyMT-induced mammary gland tumor cell stemness, tumor initiation, and growth in vivo. Slug also mediated these functions of Klf5 in vivo. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: R Liu Et Alsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 84%

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Krüpple‐like factor 5 is essential for mammary gland development and tumorigenesis

Liu

Shi

Zhou

et al. 2018

The Journal of Pathology

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“…Thus, circVRK1 was negatively correlated with stemness of BCSCs through the miR-153-5p/krüppel-like factor 5 (KLF5) regulatory pathways. 240 Stem cell plasticity and identity are also controlled by master regulatory genes and complex circuits involving circRNAs as well. One study showed that compared to differentiated mesodermal derivatives, circFOXP1 levels were enriched in mesenchymal stem cell (MSC) and silencing of circFOXP1 dramatically impaired MSC differentiation in vitro and in vivo.…”

Section: Circrnas In Cancer Stem Cellsmentioning

confidence: 99%

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

Tang

Hann

2020

OTT

133

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Circular RNA (circRNA) is an intriguing class of RNA with covalently closedloop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.

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“…Breast cancer (BC) is one of the most common malignancies in women, and its incidence is the second highest in the world (1,2).…”

Section: Introductionmentioning

confidence: 99%

Involvement of breast cancer stem cells in tumor angiogenesis

Wang

et al. 2017

Oncol Lett

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Abstract. The aim of the present study was to investigate the role of breast cancer stem cells (BCSCs) in the angiogenesis of breast cancer tumors. The expression levels of mutant p53, cluster of differentiation (CD)31, vascular endothelial factor (VEGF), in addition to human epidermal growth factor (HER)2, were detected in the blood vessels of human breast cancer (BC) tissue samples. CD44 + /CD24 -/low cells were selected from single-cell suspensions of BC tissues to assess the expression of CD31 and CD105, in addition to the ability of these cells to metabolize acetylated low-density lipoprotein (Ac-LDL). Furthermore, vascular-like structures were observed histologically. Mutant p53, CD31 and VEGF were all expressed in these tissues. CD44+ cells comprised 7.5±2.6 and 94.3±4.7% of the cell population prior to and following sorting, respectively. CD24 + cells comprised 48.2±9.4 and 4.3±4% of the cell population prior to and following sorting, respectively. A low proportion of CD24 + cells corresponded to a high proportion of CD24 -/low cells. The percentages of CD105 + and CD31 + glomus cells in the mammary gland were 4.5±0.9 and 6.2±1.3%, respectively, and following passaging for three generations, these increased to 79.6±9.3 and 84.1±10.7%, respectively (P<0.05). Cells were cultured using an endothelial cell culture system, and they internalized DiL-Ac-LDL. Here, vascular endothelial cells formed vascular-like structures, whereas the control group demonstrated no such structures. Overall, the results suggest that BCSCs-derived endothelial cells may contribute to tumor angiogenesis.

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Mifepristone Suppresses Basal Triple-Negative Breast Cancer Stem Cells by Down-regulating KLF5 Expression

Cited by 109 publications

References 53 publications

Krüpple‐like factor 5 is essential for mammary gland development and tumorigenesis

Krüpple‐like factor 5 is essential for mammary gland development and tumorigenesis

<p>Biological Roles and Mechanisms of Circular RNA in Human Cancers</p>

Involvement of breast cancer stem cells in tumor angiogenesis

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