Abstract CN12-03: Epithelial-mesenchymal transition in human breast cancer progression: cancer stem cell attributes, dissemination, and dormancy

Epithelial-mesenchymal transition (EMT) is a multistep process in which cells acquire molecular alterations such as loss of cell-cell junctions and restructuring of the cytoskeleton. There is an increasing understanding that this process may promote breast cancer progression through promotion of invasive and metastatic tumor growth. Recent observations imply that there may be a cross-talk between EMT and cancer stem cell properties, leading to enhanced tumorigenicity and the capacity to generate heterogeneous tumor cell populations. Here, we review the experimental and clinical evidence for the involvement of EMT in cancer stem cell theory, focusing on the common characteristics of this phenomenon.

Download Full-text

RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.613470 ◽

2020 ◽

Vol 10 ◽

Author(s):

Danping Wang ◽

Yifan Wang ◽

Xuebiao Wu ◽

Xiangxing Kong ◽

Jun Li ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Colony Formation ◽

Human Breast Cancer ◽

Epithelial Mesenchymal Transition ◽

Epigenetic Modification ◽

Dependent Manner ◽

Human Breast ◽

Mesenchymal Transition ◽

E Cadherin

BackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer.Experimental designWe studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses.ResultsIn this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival.ConclusionRNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer.

Download Full-text

Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells

International Journal of Molecular Sciences ◽

10.3390/ijms222212604 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12604

Author(s):

Rodrigo A. Acuña ◽

Manuel Varas-Godoy ◽

Diego Herrera-Sepulveda ◽

Mauricio A. Retamal

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Human Breast Cancer ◽

Epithelial To Mesenchymal Transition ◽

Cellular Communication ◽

Mrna Levels ◽

Human Breast ◽

Mesenchymal Transition ◽

Mcf 7

Connexins (Cxs) are a family of proteins that form two different types of ion channels: hemichannels and gap junction channels. These channels participate in cellular communication, enabling them to share information and act as a synchronized syncytium. This cellular communication has been considered a strong tumor suppressor, but it is now recognized that some type of Cxs can be pro-tumorigenic. For example, Cx46 expression is increased in human breast cancer samples and correlates with cancer stem cell (CSC) characteristics in human glioma. Thus, we explored whether Cx46 and glioma cells, can set up CSC and epithelial-to-mesenchymal transition (EMT) properties in a breast cancer cell line. To this end, we transfected MCF-7 cells with Cx46 attached to a green fluorescent protein (Cx46GFP), and we determined how its expression orchestrates both the gene-expression and functional changes associated with CSC and EMT. We observed that Cx46GFP increased Sox2, Nanog, and OCT4 mRNA levels associated with a high capacity to form monoclonal colonies and tumorspheres. Similarly, Cx46GFP increased the mRNA levels of n-cadherin, Vimentin, Snail and Zeb1 to a higher migratory and invasive capacity. Furthermore, Cx46GFP transfected in MCF-7 cells induced the release of higher amounts of VEGF, which promoted angiogenesis in HUVEC cells. We demonstrated for the first time that Cx46 modulates CSC and EMT properties in breast cancer cells and thus could be relevant in the design of future cancer therapies.

Download Full-text

Epithelial Mesenchymal Transition Traits in Human Breast Cancer Cell Lines Parallel the CD44hi/CD24lo/- Stem Cell Phenotype in Human Breast Cancer

Journal of Mammary Gland Biology and Neoplasia ◽

10.1007/s10911-010-9175-z ◽

2010 ◽

Vol 15 (2) ◽

pp. 235-252 ◽

Cited By ~ 185

Author(s):

Tony Blick ◽

Honor Hugo ◽

Edwin Widodo ◽

Mark Waltham ◽

Cletus Pinto ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Human Breast Cancer ◽

Epithelial Mesenchymal Transition ◽

Human Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Cell Phenotype ◽

Human Breast ◽

Mesenchymal Transition ◽

Stem Cell Phenotype

Download Full-text

A New Invasion and Metastasis Molecule, Tiaml and Its Interaction With the Cytoskeleton Are Involved in Human Breast Cancer Progression

10.21236/ada392244 ◽

2000 ◽

Author(s):

Lilly Y. Bourguignon

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Human Breast Cancer ◽

Breast Cancer Progression ◽

Human Breast ◽

Invasion And Metastasis

Download Full-text

Proteomic Portrait of Human Breast Cancer Progression Identifies Novel Prognostic Markers

Cancer Research ◽

10.1158/0008-5472.can-11-3711 ◽

2012 ◽

Vol 72 (9) ◽

pp. 2428-2439 ◽

Cited By ~ 88

Author(s):

Tamar Geiger ◽

Stephen F. Madden ◽

William M. Gallagher ◽

Juergen Cox ◽

Matthias Mann

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Human Breast Cancer ◽

Prognostic Markers ◽

Breast Cancer Progression ◽

Human Breast

Download Full-text

RUNX1 suppresses breast cancer stemness and tumor growth

10.1101/315093 ◽

2018 ◽

Author(s):

Deli Hong ◽

Andrew J. Fritz ◽

Kristiaan H. Finstad ◽

Mark P. Fitzgerald ◽

Adam L. Viens ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Tumor Suppressor ◽

Cancer Stem Cell ◽

Tumor Growth ◽

Epithelial Mesenchymal Transition ◽

Ectopic Expression ◽

Cell Activity ◽

Mesenchymal Transition

SummaryRecent studies have revealed that mutations in the transcription factor Runx1 are prevalent in breast tumors. Yet, how loss of Runx1 contributes to breast cancer (BCa) remains unresolved. We demonstrate for the first time that Runx1 represses the breast cancer stem cell (BCSC) phenotype and consequently, functions as a tumor suppressor in breast cancer. Runx1 ectopic expression in MCF10AT1 and MCF10CA1a BCa cells reduces (60%) migration, invasion and in vivo tumor growth in mouse mammary fat pad (P<0.05). Runx1 is decreased in BCSCs, and overexpression of Runx1 suppresses tumorsphere formation and reduces the BCSC population. Furthermore, Runx1 inhibits Zeb1 expression, while Runx1 depletion activates Zeb1 and the epithelial-mesenchymal transition. Mechanistically Runx1 functions as a tumor suppressor in breast cancer through repression of cancer stem cell activity. This key regulation of BCSCs by Runx1 may be shared in other epithelial carcinomas, highlighting the importance of Runx1 in solid tumors.

Download Full-text

Adipose-derived stem cells enhance human breast cancer growth and cancer stem cell-like properties through adipsin

Oncogene ◽

10.1038/s41388-018-0477-8 ◽

2018 ◽

Vol 38 (6) ◽

pp. 767-779 ◽

Cited By ~ 22

Author(s):

Hideaki Goto ◽

Yohei Shimono ◽

Yohei Funakoshi ◽

Yoshinori Imamura ◽

Masanori Toyoda ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cell ◽

Human Breast Cancer ◽

Cancer Growth ◽

Adipose Derived Stem Cells ◽

Human Breast ◽

Breast Cancer Growth

Download Full-text

LINC00665 promotes breast cancer progression through regulation of the miR-379-5p/LIN28B axis

Cell Death and Disease ◽

10.1038/s41419-019-2213-x ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Wei Ji ◽

Yu-Ling Diao ◽

Yi-Ran Qiu ◽

Jie Ge ◽

Xu-Chen Cao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Normal Breast ◽

Breast Cancer Progression ◽

Migration And Invasion ◽

Breast Tumorigenesis ◽

Mesenchymal Transition ◽

Tumorigenesis And Progression ◽

Mirna Sponges

AbstractBreast cancer is the most common malignant tumor among women worldwide. Although increasing evidence indicates that long noncoding RNAs (lncRNAs) play critical roles during breast tumorigenesis and progression, the involvement of most lncRNAs in breast cancer remains largely unknown. In the current study, we demonstrated that LINC00665 promotes breast cancer cell proliferation, migration, and invasion. Accumulating evidence indicates that many lncRNAs can function as endogenous miRNA sponges by competitively binding common miRNAs. In this study, we demonstrated that LINC00665 functions as a sponge for miR-379-5p, reducing the ability of miR-379-5p to repress LIN28B. LINC00665 promoted breast cancer progression and induced an epithelial–mesenchymal transition-like phenotype via the upregulation of LIN28B expression. Clinically, LINC00665 expression was increased but miR-379-5p expression was decreased in breast cancer tissues compared with that in normal breast tissues in the TCGA database. Furthermore, the expression of LINC00665 was negatively related with miR-379-5p expression. Collectively, our results reveal the LINC00665–miR-379-5p–LIN28B axis and shed light on breast cancer therapy.

Download Full-text

Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer

Cancers ◽

10.3390/cancers12010029 ◽

2019 ◽

Vol 12 (1) ◽

pp. 29 ◽

Cited By ~ 3

Author(s):

Jyun-Yuan Huang ◽

Yen-Yun Wang ◽

Steven Lo ◽

Ling-Ming Tseng ◽

Dar-Ren Chen ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Progression ◽

Human Breast Cancer ◽

Breast Cancer Progression ◽

Akt Pathway ◽

Adipose Derived Stem Cells ◽

Human Breast ◽

Akt Inhibitor ◽

Promoting Effect

Adipose-derived stem cells (ADSCs) have been implicated in tumor growth and metastasis in breast cancer. ADSCs exhibit tumor tropism, and are of increasing clinical relevance due to the autologous fat grafting for breast reconstruction. Although we have previously shown that a high level of the adipocytokine visfatin in human breast cancer tissues correlated with tumor progression mediated by cAbl and STAT3, the effects of visfatin in the tumor microenvironment are unclear. To understand how visfatin modulates breast cancer within the tumor-stromal environment, we examined determinants of breast cancer progression using a visfatin-primed ADSCs-tumor co-culture model. ADSCs were isolated from tumor-free adipose tissue adjacent to breast tumors. ADSCs were treated with or without visfatin for 48 h and then collected for co-culture with breast cancer cell line MDA-MB-231 for 72 h in a transwell system. We found that the MDA-MB-231 cells co-cultured with visfatin-treated ADSCs (vADSCs) had higher levels of cell viability, anchorage independent growth, migration, invasion, and tumorsphere formation than that co-cultured with untreated ADSCs (uADSCs). Growth differentiation factor 15 (GDF15) upregulation was found in the co-culture conditioned medium, with GDF15 neutralizing antibody blocking the promoting effect on MDA-MB-231 in co-culture. In addition, a GDF15-induced AKT pathway was found in MDA-MB-231 and treatment with PI3K/AKT inhibitor also reversed the promoting effect. In an orthotopic xenograft mouse model, MDA-MB-231 co-injected with vADSCs formed a larger tumor mass than with uADSCs. Positive correlations were noted between visfatin, GDF15, and phosphor-AKT expressions in human breast cancer specimens. In conclusion, visfatin activated GDF15-AKT pathway mediated via ADSCs to facilitate breast cancer progression.

Download Full-text