Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

Yue, Dongli; Zhang, Zhen; Li, Jieyao; Chen, Xinfeng; Yü, Ping; Li, Shasha; Shi, Xiaojuan; Li, Lifeng; Wang, Liping; Huang, Lan; Zhang, Bin; Sun, Yan; Zhang, Yi

doi:10.1016/j.yexcr.2015.06.007

Cited by 39 publications

(35 citation statements)

References 43 publications

(62 reference statements)

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“…A growing body of evidence demonstrates that SOX2, ALDH1A1 and NANOG are important stemness genes for many CSCs and play crucial roles in self-renewing, differentiation and tumorigenicity of CSCs [29, 30]. RSPO2 is a member of the R-spondin family proteins that are secreted agonists of the canonical Wnt pathway, which act through binding with LGRs.…”

Section: Resultsmentioning

confidence: 99%

Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma

Zhang

et al. 2017

Oncotarget

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Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated cells with biological characteristics that include the capacity for self-renewal, differentiation into various lineages, and tumor initiation. To explore the mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene of the Wnt signaling pathway, which has been identified as a marker of intestinal stem cells and shown to be overexpressed in several human malignancies. Lgr5 expression was significantly correlated with lymph node metastasis, increased depth of invasion, increased tumor size, advanced differentiation, higher AJCC stage and poorer survival. Silencing of Lgr5 expression in the ESCC cell line KYSE450 by small interfering RNA (siRNA) strongly inhibited cell proliferation, migration and invasion ability, the expression of CSCs-related genes and Wnt/β-catenin signaling. In addition, Lgr5 was highly expressed in ESCC spheroid body cells, which were identified by high expression of CSCs-related genes, and high tumorigenicity in vivo. Taken together, these results demonstrate that Lgr5 activation of Wnt/β-catenin signaling is a potential mechanism to promote the progression of ESCC and ESCC stem cell renewal, and Lgr5 may be used as a molecular target for the development of treatments for ESCC.

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Section: Resultsmentioning

confidence: 99%

Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma

Zhang

et al. 2017

Oncotarget

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“…Statistical analyses were conducted using the SPSS software, version 19.0 (SPSS). All data were expressed as the mean ± SD.…”

Section: Discussionmentioning

confidence: 99%

“…The stably transfected cells were generated according to previous studies 14,18 and then treated with 10 μg/mL puromycin for 48 hours. 19 19 …”

Section: Lgr5 + Cd44 + Epcam + Cells Culture and Infectionmentioning

confidence: 99%

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

Leng

Zhou

et al. 2019

J Cellular Molecular Medi

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| INTRODUC TI ONCancer metastasis contributes to approximately 90% of cancer-related deaths. 1 Accumulating evidence indicates that cancer stem cells (CSCs) are responsible for the seeding and colonization of cancer metastasis. 2-4 For the past decades, studies have explored and investigated the mechanisms of human carcinogenesis to help develop novel therapeutic strategies. To date, cancer treatment has not been much improved in advanced and chemo-resistant human cancers. Thus, a better understanding of CSCs behaviour in human cancers, including colorectal cancers (CRC), could provide insight into defining the molecular mechanisms of tumorigenesis and cancer progression. Indeed, identification of CSC markers is a very hot topic and interesting data have been generated. 5 For example, CSC markers for breast, prostate, AbstractKrüppel-like factor 4 (KLF4) was closely associated with epithelial-mesenchymal transition and stemness in colorectal cancer stem cells (CSCs)-enriched spheroid cells.Nonetheless, the underlying molecular mechanism is unclear. This study showed that KLF4 overexpression was accompanied with stemness and mesenchymal features in Lgr5 + CD44 + EpCAM + colorectal CSCs. KLF4 knockdown suppressed stemness, mesenchymal features and activation of the TGF-β1 pathway, whereas enforced KLF4 overexpression activated TGF-β1, phosphorylation of Smad 2/3 and Snail expression, and restored stemness and mesenchymal phenotypes. Furthermore, TGF-β1 pathway inhibition invalidated KLF4-facilitated stemness and mesenchymal features without affecting KLF4 expression. The data from the current study are the first to demonstrate that KLF4 maintains stemness and mesenchymal properties through the TGF-β1/Smad/Snail pathway in Lgr5 + CD44 + EpCAM + colorectal CSCs. K E Y W O R D Scancer stem cell, colorectal cancer, Krüppel-like factor 4, snail, TGF-β1

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“…TGF-β1 and EGFR, known TFs, may play significant roles in the progression of ESCA. TGF-β1 promotes the invasion and migration of sphere-forming stem-like cells in esophageal cancer [60]. TGF-β1 also induced the epithelial to mesenchymal transition (EMT) via the regulation of PTEN/PI3K signaling pathway in ESCC [61].…”

Section: Discussionmentioning

confidence: 99%

Identification of molecular targets for esophageal carcinoma diagnosis using miRNA-seq and RNA-seq data from The Cancer Genome Atlas: a study of 187 cases

et al. 2017

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Esophageal carcinoma (ESCA) is one of the most common malignancies worldwide, and its pathogenesis is complex. In this study, we identified differentially expressed miRNAs (DEMs) and genes (DEGs) of ESCA from The Cancer Genome Atlas (TCGA) database. The diagnostic values of DEMs were determined by receiver operating characteristic (ROC) analyses and validated based on data from Gene Expression Omnibus (GEO). The top five DEMs with the best diagnostic values were selected, and their potential targets were predicted by various in silico methods. These target genes were then identified among the DEGs from TCGA. Furthermore, the overlapping genes were subjected to protein-protein interaction (PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The miRNA-transcription factor (TF) regulatory relations were determined using CircuitsDB and TransmiR. Finally, the regulatory networks of miRNA-TF and miRNA-gene were constructed and analyzed. A total of 136 DEMs and 3541 DEGs were identified in ESCA. The top five DEMs with the highest area under the receiver operating characteristic curve (AUC) values were miRNA-93 (0.953), miRNA-21 (0.928), miRNA-4746 (0.915), miRNA-196a-1 (0.906) and miRNA-196a-2 (0.906). The combined AUC of these five DEMs was 0.985. The KEGG analysis with 349 overlapping genes showed that the calcium signaling pathway and the neuroactive ligand-receptor interaction were the most relevant pathways. The regulatory networks of miRNA-TF and miRNA-gene, including 38 miRNA-TF and 560 miRNA-gene pairs, were successfully established. Our findings may provide new insights into the molecular mechanisms of ESCA pathogenesis. Future research will aim to explore the role of novel miRNAs in the pathogenesis and improve the early diagnosis of ESCA.

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Transforming growth factor-beta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer

Cited by 39 publications

References 43 publications

Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma

Expression and functional regulation of stemness gene Lgr5 in esophageal squamous cell carcinoma

Krüppel‐like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF‐β1/Smad/snail pathway

Identification of molecular targets for esophageal carcinoma diagnosis using miRNA-seq and RNA-seq data from The Cancer Genome Atlas: a study of 187 cases

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