Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis

Chen, Hsiao-Fan; Huang, Chih Chia; Liu, Chung Ji; Hung, Jan Jong; Hsu, Chih Chin; Teng, Shu-Chun; Wu, Kou Juey

doi:10.1038/ncomms5697

Cited by 71 publications

(66 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Activin A or TGF-β upregulates several transcription factors such as SNAI2, ZEB1 or TWIST1 mediated by phosphorylated SMAD2 or SMAD3 (Lamouille et al 2014, Li et al 2015. NOTCH signaling upregulates the SMAD3 expression, which enhances TGF-β-induced EMT markers expression (Niessen et al 2008, Fu et al 2009, Chen et al 2014. These findings suggest that attachment of TE (CT-1) cells to EECs could activate the NOTCH signaling, which enhances activin A-induced EMT marker expression via SMAD2, SMAD3 and/or SMAD4.…”

Section: Regulation Of Emt-related Molecule Expression During the Permentioning

confidence: 67%

Continuous model of conceptus implantation to the maternal endometrium

Imakawa

Bai

Fujiwara

et al. 2017

Journal of Endocrinology

View full text Add to dashboard Cite

As placental morphology as well as trophoblast characteristics exhibit wide diversity across mammalian species, underling molecules were also thought to vary greatly. In the majority of cases, however, regardless of the mode of implantation, physiological and biochemical processes in conceptus implantation to the maternal endometrium including the kinds of gene expression and their products are now considered to share many similarities. In fact, recent progress has identified that in addition to the hormones, cytokines, proteases and cell adhesion molecules classically characterized, molecules related to lymphocyte homing and epithelial-mesenchymal transition (EMT) are all required for the progression of conceptus implantation to placentation. In this review, therefore, the newest findings are all incorporated into the molecular and cellular events related to conceptus implantation to the maternal endometrium; primarily from non-invasive bovine placentation and also from invasive human implantation.

show abstract

Section: Regulation Of Emt-related Molecule Expression During the Permentioning

confidence: 67%

Continuous model of conceptus implantation to the maternal endometrium

Imakawa

Bai

Fujiwara

et al. 2017

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…First, miRNA treatments induced ZEB1 suppression in xenograft tumors, highlighting the ability of miR-9 and miR-200 to regulate not only tumor-mediated vasculogenesis but also, more generally, EMT. Interestingly, Twist1, another key transcriptional factor that triggers EMT, was recently reported to induce the endothelial transition of tumor cells (39). Moreover, this approach represents a proof of concept for exploiting miR-9 and miR-200 as therapeutic tools to affect tumor vascularization.…”

Section: Discussionmentioning

confidence: 99%

miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer

et al. 2016

View full text Add to dashboard Cite

Organization of cancer cells into endothelial-like cell-lined structures to support neovascularization and to fuel solid tumors is a hallmark of progression and poor outcome. In triple-negative breast cancer (TNBC), PDGFRb has been identified as a key player of this process and is considered a promising target for breast cancer therapy. Thus, we aimed at investigating the role of miRNAs as a therapeutic approach to inhibit PDGFRb-mediated vasculogenic properties of TNBC, focusing on miR-9 and miR-200. In MDA-MB-231 and MDA-MB-157 TNBC cell lines, miR-9 and miR-200 promoted and inhibited, respectively, the formation of vascular-like structures in vitro. Induction of endogenous miR-9 expression, upon ligand-dependent stimulation of PDGFRb signaling, promoted significant vascular sprouting of TNBC cells, in part, by direct repression of STARD13. Conversely, ectopic expression of miR-200 inhibited this sprouting by indirectly reducing the protein levels of PDGFRb through the direct suppression of ZEB1. Notably, in vivo miR-9 inhibition or miR-200c restoration, through either the generation of MDA-MB-231-stable clones or peritumoral delivery in MDA-MB-231 xenografted mice, strongly decreased the number of vascular lacunae. Finally, IHC and immunofluorescence analyses in TNBC specimens indicated that PDGFRb expression marked tumor cells engaged in vascular lacunae. In conclusion, our results demonstrate that miR-9 and miR-200 play opposite roles in the regulation of the vasculogenic ability of TNBC, acting as facilitator and suppressor of PDGFRb, respectively. Moreover, our data support the possibility to therapeutically exploit miR-9 and miR-200 to inhibit the process of vascular lacunae formation in TNBC. Cancer Res; 76(18); 5562-72. Ó2016 AACR.

show abstract

“…However, we focus on a novel source of ECs, which is derived from tumor cells directly. Several initial reports have shown the generation of ECs from malignant cells in lymphomas [26], neuroblastoma [7], head and neck cancer [27] and breast cancer [28]. These kinds of cells have the following characteristics.…”

Section: Discussionmentioning

confidence: 99%

ETS-1 Induces Endothelial-Like Differentiation and Promotes Metastasis in Non-Small Cell Lung Cancer

Zhou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Recently, endothelial-like cells originating directly from tumor cells have been revealed. However, the mechanism remains unclear. ETS-1 (E26 transformation specific-1), a key transcription factor in the generation and maturation of ECs (endothelial cells), has been reported to be overexpressed in several cancers. Here, we reveal novel regulation of the endothelial-like differentiation of NSCLC (non-small cell lung cancer) cells by ETS-1. Methods: We up-regulated the expression of ETS-1 in NSCLC cell lines by H₂O₂ or lentiviral vector. Endothelial phenotypes, such as vWF (von Willebrand factor) and VE-cadherin were examined by Western blot analysis and immunofluorescence assay. Tube formation assay and phagocytotic activity assay were performed to evaluate ECs’ specific features on NSCLC cells. The effect of ETS-1 on metastasis was determined by wound healing assays, transwell assays and a xenograft tumor model. To explore the role of ETS-1 in the initiation and progression of NSCLC, we examined ETS-1 levels in NSCLC cancerous tissues and paired adjacent normal tissues by immunohistochemstry and analyzed the relationship between ETS-1 levels and clinicopathological parameters, as well as patient survival. Kaplan Meier plotter database was used to assess the prognostic value of ETS-1 in NSCLC. The association between ETS-1 levels and MVD (microvessel density) was analyzed to determine their role in angiogenesis. Results: With ETS-1 up-regulation, the expression of vWF and VE-cadherin was increased in NSCLC cells. Additionally, cells adopted several ECs’ specific features, including enhanced tube formation ability and uptake of Dil-ac-LDL (acetylated low-density lipoprotein) and lectin. ETS-1 up-regulation also promoted cell migration, invasion and adhesion. In addition, xenograft mice arising from ETS-1 over-expressing cells had more liver metastases. In the clinical specimens, ETS-1 expression was significantly higher in NSCLC cancerous tissues than adjacent nontumorous tissues and positively associated with tumor size, T stage, N stage and clinical stage. Patients with high levels of ETS-1 expression had significantly poorer OS (overall survival) and FP (first progression) than those with low expression. Furthermore, there was a positive correlation between ETS-1 level and MVD. Conclusion: Collectively, our data reveal that ETS-1 can induce the differentiation of tumor cells into endothelial-like cells and further promote metastatic dissemination in NSCLC.

show abstract

Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis

Cited by 71 publications

References 48 publications

Continuous model of conceptus implantation to the maternal endometrium

Continuous model of conceptus implantation to the maternal endometrium

miR-9 and miR-200 Regulate PDGFRβ-Mediated Endothelial Differentiation of Tumor Cells in Triple-Negative Breast Cancer

ETS-1 Induces Endothelial-Like Differentiation and Promotes Metastasis in Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About