EMT-induced stemness and tumorigenicity are fueled by an oncogenic EGF/Ras pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Tuan Zea Tan
PROVIDER: E-GEOD-44055 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
EMT-induced stemness and tumorigenicity are fueled by the EGFR/Ras pathway.
Voon Dominic Chih-Cheng DC Wang Huajing H Koo Jason Kin Wai JK Chai Juin Hsien JH Hor Yit Teng YT Tan Tuan Zea TZ Chu Yeh-Shiu YS Mori Seiichi S Ito Yoshiaki Y
PloS one 20130812 8
Recent studies have revealed that differentiated epithelial cells would acquire stem cell-like and tumorigenic properties following an Epithelial-Mesenchymal Transition (EMT). However, the signaling pathways that participate in this novel mechanism of tumorigenesis have not been fully characterized. In Runx3 (-/-) p53 (-/-) murine gastric epithelial (GIF-14) cells, EMT-induced plasticity is reflected in the expression of the embryonal proto-oncogene Hmga2 and Lgr5, an exclusive gastrointestinal ...[more]
Similar Datasets
Project description:Pre-EMT GIF14 cells treated with TGF-β1
2014-02-19 | GSE44055 | GEO
Project description:This study aimed to establish an epithelial-mesenchymal transition (EMT) model with an immortalized human bronchial epithelial cell line, M-BE, and to identify an EMT signature gene set. The TGF-M-NM-21-induced M-BE cells got spindle-shaped fibroblast-like morphology and lost the cell-cell contact, with down-regulated expression of epithelial marker E-cadherin and up-regulated expression of mesenchymal markers N-cadherin and Vimentin. Examined by microarray, there were 2628 genes identified as significant EMT-related, including 1490 up-regulated genes (FC > 2, fdr < 0.01) and 1138 down-regulated genes (FC < 0.5, fdr < 0.01) in TGF-M-NM-21-induced M-BE cells. M-BE cells were treated with human recombinant TGF-M-NM-21 (5ng/ml) for six days. M-BE cells cultured without TGF-M-NM-21 were considered the controls. Three replicates of each were carried out for this investigation. Agilent 4x44K Human Whole Genome expression microarray (G4112F) analysis was applied to the RNA samples of the TGF-M-NM-21-treated M-BE cells and the controls.
2013-10-06 | E-GEOD-40374 | biostudies-arrayexpress
Project description:Recent studies have revealed that differentiated epithelial cells would acquire stem cell-like and tumorigenic properties following an Epithelial-Mesenchymal Transition (EMT). However, the signaling pathways that participate in this novel mechanism of tumorigenesis have not been fully characterized. In Runx3 (-/-) p53 (-/-) murine gastric epithelial (GIF-14) cells, EMT-induced plasticity is reflected in the expression of the embryonal proto-oncogene Hmga2 and Lgr5, an exclusive gastrointestinal stem cell marker. Here, we report the concurrent activation of an EGFR/Ras gene expression signature during TGF-?1-induced EMT in GIF-14 cells. Amongst the altered genes was the induction of Egfr, which corresponded with a delayed sensitization to EGF treatment in GIF-14. Co-treatment with TGF-?1 and EGF or the expression of exogenous KRas led to increased Hmga2 or Lgr5 expression, sphere initiation and colony formation in soft agar assay. Interestingly, the gain in cellular plasticity/tumorigenicity was not accompanied by increased EMT. This uncoupling of EMT and the induction of plasticity reveals an involvement of distinct signaling cues, whereby the EGFR/Ras pathway specifically promotes stemness and tumorigenicity in EMT-altered GIF-14 cells. These data show that the EGFR/Ras pathway requisite for the sustenance of gastric stem cells in vivo and in vitro is involved in the genesis and promotion of EMT-induced tumor-initiating cells.
| S-EPMC3741305 | biostudies-literature
Project description:To investigate the role of TGF-M-NM-21-regulated miRNAs in the progression of colorectal cancer,we performed comprehensive miRMA microarray analysis on RNA derived from typical human colorectal cancer cell lines and TGF-M-NM-21 knock-down human colorectal cancer cell lines. We identified a novel set of TGF-M-NM-21-related miRNAs. Total RNA was isolated from TGF-M-NM-21-knock down colorecatl cancer cell lines and controls.Three-condition experiment: shRNA-TGF-M-NM-21/Lovo cells vs. shRNA-Control/Lovo cells, shRNA-TGF-M-NM-21/SW620 cells vs. shRNA-Control/ SW620 cells, and shRNA-TGF-M-NM-21/HT29 cells vs. shRNA-Control/HT29 cells. Biological replicates: 1 Lovo cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo, 1SW620 cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo, 1HT29 cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo, 1Love cells stably transfected with shRNA-Control- pSUPER gfp-neo, 1SW620 cells stably transfected with shRNA-Control- pSUPER gfp-neo, and 1HT29 cells stably transfected with shRNA-Control- pSUPER gfp-neo, independently grown and harvested. One replicate per array.
2013-12-16 | E-GEOD-53338 | biostudies-arrayexpress
Project description:To investigate the role of TGF-M-NM-21-regulated miRNAs in the progression of RMS,we performed comprehensive miRMA microarray analysis on RNA derived from typical RMS cell lines and TGF-M-NM-21 knock-down cell lines. We identified a novel set of TGF-M-NM-21-related miRNAs. Total RNA was isolated from TGF-M-NM-21-knock down rhabdmyosarcoma cell lines and controls. Three-condition experiment: shRNA-TGF-M-NM-21/RD cells vs. shRNA-Control/RD cells, shRNA-TGF-M-NM-21/SMS-CTR cells vs. shRNA-Control/ SMS-CTR cells, and shRNA-TGF-M-NM-21/RH28 cells vs. shRNA-Control/RH28 cells. Biological replicates: 1 RD cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo, 1SMS-CTR cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo, 1RH28 cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo, 1RD cells stably transfected with shRNA-Control- pSUPER gfp-neo, 1SMS-CTR cells stably transfected with shRNA-Control- pSUPER gfp-neo, and 1RH28 cells stably transfected with shRNA-Control- pSUPER gfp-neo, independently grown and harvested. One replicate per array.
2012-09-13 | E-GEOD-40843 | biostudies-arrayexpress
Project description:To investigate the role of TGF-M-NM-21-regulated miRNAs in the progression of colorectal cancer,we performed comprehensive miRMA microarray analysis on RNA derived from CT26 cell lines and TGF-M-NM-21 knock-down CT26 cell lines. We identified a novel set of TGF-M-NM-21-related miRNAs. Total RNA was isolated from TGF-M-NM-21-knock down CT26 cell lines and controls.Three-condition experiment: Locked nucleic acid microarray analyses to obtain miRNA expression profiles independently in TGFM-NM-21-knocked down CT26 and control cell line at three different time (24hours, 48hours and 72hours).Biological replicates: 1 CT26 cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo for 24hours, 1 CT26 cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo for 48hours, 1 CT26 cells stably transfected with shRNA-TGF-M-NM-21- pSUPER gfp-neo for 72hours, 1 CT26 cells stably transfected with shRNA-Control- pSUPER gfp-neo for 24hours, 1 CT26 cells stably transfected with shRNA- Control- pSUPER gfp-neo for 48hours, 1 CT26 cells stably transfected with shRNA-Control- pSUPER gfp-neo for 72hours, independently grown and harvested. One replicate per array.
2013-12-16 | E-GEOD-53337 | biostudies-arrayexpress
Project description:Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA) -related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) in NSCLC. MiRNA expression profiles were examined before and after transforming growth factor-beta1 (TGF-M-NM-21) exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. MiRNA array and quantitative RT-PCR revealed that TGF-M-NM-21 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcinoma cells with EMT. MAGI2 (membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2), a predicted target of these miRNAs and a scaffold protein required for PTEN (phosphatase and tensin homolog), was diminished in A549 cells with EMT after the TGF-M-NM-21 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-M-NM-21-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-M-NM-21-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, whose suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be new therapeutic targets in advanced lung adenocarcinoma patients, depending on the EMT phenomenon. miRNA expression profiles before and after TGF-M-NM-21 exposure were assessed in the four lung adenocarcinoma cell lines, A549, LC2/ad, PC3, and, PC9 by TaqMan miRNA arrays. Relative ratios of miRNAs in cells after TGF-M-NM-21 exposure were calculated when compared with the cells before TGF-M-NM-21 exposure.
2013-10-30 | E-GEOD-51828 | biostudies-arrayexpress
Project description:BackgroundPrevious studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown.ResultsWe show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells.ConclusionsWe suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.
| S-EPMC7814647 | biostudies-literature
Project description:The role of TGF-M-NM-2-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination is well established, but the involvement of lncRNAs in TGF-M-NM-2 signaling is still unknown. In this study, we observed that the lncRNA-Activated by TGF-M-NM-2 (lncRNA-ATB) was upregulated in hepatocellular carcinoma (HCC) metastases and associated with poor prognosis. lncRNA-ATB promotes the invasion-metastasis cascade, which suggest that lncRNA-ATB, a mediator of TGF-M-NM-2 signaling, could predispose HCC patients to metastases and may serve as a potential target for anti-metastatic therapies. SMMC-7721 hepatoma cells were continuously treated with 10 ng/ml of recombinant TGF-M-NM-21 for 21 days. Total RNA recovered from three untreated cells and three treated cells were used to acquire different expression profiles of mRNAs and lncRNAs.
2014-02-08 | E-GEOD-54797 | biostudies-arrayexpress
Project description:Langerhans dendritic cells represent abundantly occuring and evolutionary highly conserved DCs specifically located in the stratified epithelial tissues. LCs are unique among DC family members in that they express epithelial-type adhesion molecules, allowing them to form a tight three-dimensional network in basal and suprabasal epidermal keratinocyte layers and developmentally dependent on the cytokine TGF-M-NM-21. In the present study, we identified BMP-7 as another key factor inducing LC differnetiation. Here we have performed comparative analysis of highly purified CD207+/CD1a+ in vitro generated Langerhans cells in the presence of BMP-7 and TGF-M-NM-21. We have identified that both BMP-7-LCs and TGF-M-NM-21-LCs are closely related to each other. CD34+ hematopoietic stem cells were isolated from freshly obtained cord blood and cultured in the presence of GM-CSF, SCF, Flt3L, TNFa and either TGF-M-NM-21 or BMP-7 for 7 days to get immature LCs. RNA was isolated from these in vitro genetared LCs.
2013-10-18 | E-GEOD-49085 | biostudies-arrayexpress