Cancer-associated fibroblasts induce epithelial–mesenchymal transition of breast cancer cells through paracrine TGF-β signalling

Yu, Yingying; Xiao, Changlai; Tan, Li; Wang, Q. S.; Li, X. Q.; Feng, Yuanming

doi:10.1038/bjc.2013.768

Cited by 519 publications

(396 citation statements)

References 30 publications

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“…[99][100][101] These molecules can be internalized directly by stromal and Figure 3 (a) Clonogenic spheres derived from a single anaplastic thyroid carcinoma cell as previously reported. 37 The cells were separated into ALDEFLUOR-positive and -negative cells by flow cytometry and cell sorting.…”

Section: Role Of the Microenvironment And Exosomes In Emt And Cscsmentioning

confidence: 81%

“…It has been shown that CAFs facilitate aggressive phenotype of breast cancer cell lines by induction of EMT by TGFβ in a paracrine manner. 99 Other studies have shown that metastatic lung cells were regulated by miR-200 expression and were responsive to TGFβ. 100,101 Metastatic lung cancer cells alternated between epithelial and mesenchymal states and formed polarized epithelial spheres in 3D culture in the presence of TGFβ.…”

Section: Role Of the Microenvironment And Exosomes In Emt And Cscsmentioning

confidence: 99%

“…98 Exosomes, which are an important part of the microenvironment, range in size from 40 to 150 nm and represent a subset of multi-vesicular bodies (MVB). [97][98][99][100][101][102][103][104][105][106][107] They are formed by inward budding of the limiting membrane of MVB and are released from the cell into the extracellular environment upon fusion of the MVB and the plasma membrane. Exosomes contain a concentrated group of functional molecules including proteins, lipids, mRNAs, non-coding RNAs and DNA molecules.…”

Section: Role Of the Microenvironment And Exosomes In Emt And Cscsmentioning

confidence: 99%

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The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

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The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

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Section: Role Of the Microenvironment And Exosomes In Emt And Cscsmentioning

confidence: 81%

Section: Role Of the Microenvironment And Exosomes In Emt And Cscsmentioning

confidence: 99%

Section: Role Of the Microenvironment And Exosomes In Emt And Cscsmentioning

confidence: 99%

See 1 more Smart Citation

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Cell viability was calculated as the value relative to control cultures. The invasion and migration of breast cells in vitro were assessed using Matrigel-coated and uncoated Transwell inserts (BD Biosciences), respectively, as described previously (15). The number of invading or migrating cells was counted in five predetermined fields for each membrane using a microscope at ϫ400 magnification.…”

Section: Rna Extraction and Quantitative Rt-pcr (Qrt-pcr)-mentioning

confidence: 99%

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

Tian

Lun

Huang

et al. 2015

Journal of Biological Chemistry

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Background: Promoter hypermethylation affects the regulation of transcription factors for target genes. Results: SP1 activates FOXF2 transcription, but this activation is prevented through FOXF2 promoter methylation. Conclusion: FOXF2 transcription is regulated through the combined effects of DNA methylation and SP1 transcriptional regulation. Significance: Herein, we describe a new regulatory mechanism for the subtype-specific expression of FOXF2 in breast cancer.

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“…In breast cancer, TGFβ1 is upregulated compared to its adjacent nonmalignant tissue and it impacts on various cells of the tumor microenvironment. In the tumor stroma, TGFβ1 gets secreted by tumor‐associated macrophages and CAFs (Kojima et al ., 2010; Yu et al ., 2014). It has been shown that TGFβ1 directly acts on the basal‐like breast tumor cell line MDA‐MB‐231 and that this drives metastatic processes of breast cancer cells by its binding to TGFBR2 (Willis et al ., 2015).…”

Section: Discussionmentioning

confidence: 99%

TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer

et al. 2018

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Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer. In this study, we performed genomewide correlation analysis of TGFBR2 expression in a panel of 51 breast cancer cell lines and identified that MET is coregulated with TGFBR2. This correlation was confirmed at the protein level in breast cancer cell lines and human tumor tissues. Flow cytometric analysis of luminal and basal‐like breast cancer cell lines and examination of 801 tumor specimens from a prospective cohort of breast cancer patients using reverse phase protein arrays revealed that expression of TGFBR2 and MET is increased in basal‐like breast cancer cell lines, as well as in triple‐negative breast cancer tumor tissues, compared to other subtypes. Using real‐time cell analysis technology, we demonstrated that TGFβ1 triggered hepatocyte growth factor (HGF)‐induced and MET‐dependent migration in vitro. Bioinformatic analysis predicted that TGFβ1 induces expression of C‐ets‐1 as a candidate transcription factor regulating MET expression. Indeed, TGFβ1‐induced expression of ETS1 and breast cancer cell migration was blocked by knockdown of ETS1. Further, we identified that MET is a direct target of miR‐128‐3p and that this miRNA is negatively regulated by TGFβ1. Overexpression of miR‐128‐3p reduced MET expression and abrogated HGF‐induced cell migration of invasive breast cancer cells. In conclusion, we have identified that TGFβ1 regulates HGF‐induced and MET‐mediated cell migration, through positive regulation of C‐ets‐1 and negative regulation of miR‐128‐3p expression in basal‐like breast cancer cell lines and in triple‐negative breast cancer tissue.

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Cancer-associated fibroblasts induce epithelial–mesenchymal transition of breast cancer cells through paracrine TGF-β signalling

Cited by 519 publications

References 30 publications

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells

TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer

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