Transforming growth factor (TGF)- plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF--induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF--induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses.
Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.
Specimen part
View SamplesDNA methylation has been considered to play an important role during myogenic differentiation. In terminal differentiation of myoblasts, chronological alteration of DNA methylation status was poorly understood. Using Infinium HumanMethylation450 BeadChips, we validated genome wide DNA methylation profiles of human myoblast differentiation models. To investigate correlation between DNA methylation and gene expression, we also assessed gene expression of myoblasts with GeneChip Human Genome U133 Plus 2.0 array.
DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation.
Sex, Age, Race
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Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence.
Sex, Age, Specimen part
View SamplesIntroduction: The majority of pulmonary carcinoid (PC) tumors can be cured by surgical resection alone, but a significant proportion of patients experience recurrences. PC is insensitive to conventional chemotherapy, and it would be necessary to reveal the molecular mechanisms of metastasis and develop targeted therapeutics.
Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence.
Sex, Age, Specimen part
View SamplesNon-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitor. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC1 cells, namely EBC1-R cells. EBC1-R cells showed overexpression of ATP-binding cassette sub-family B member 1 (ABCB1) as well as phosphorylation of MET. EBC1-R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial mesenchymal transition (EMT). The levels of two miRNAs, miR-374a and miR-138 which targeted ABCB1, were decreased in EBC1-R cells. ABCB1 siRNA and ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse the resistance to PHA-665752 in EBC1-R cells. Our study demonstrated that ABCB1 overexpression which was associated with CSC properties and EMT was involved in the acquired resistance to MET inhibitor. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitor.
Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET Inhibitors in Non-Small Cell Lung Cancer.
Cell line
View SamplesIn order to ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the anti-tumour effects of Trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via MTT assay. TSA and vorinostat both displayed strong anti-tumor activities in a proportion of NSCLC cell lines, and suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001).
Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model.
No sample metadata fields
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A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
Specimen part, Cell line, Treatment
View SamplesWe determined and analyzed the effect of TTF-1/NKX2-1 on Smad3/Smad4 binding sites by ChIP-sequencing.
A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
Specimen part, Cell line
View SamplesTTF-1/NKX2-1 was expressed by adenoviral vector and changes in gene expression were determined by RNA-sequencing. Overall design: A549 cells were infected with Ad-TTF-1 or Ad-LacZ vectors and stimulated with TGF-beta for 24 hours or left untreated. Expression of polyA RNA was determined.
A Smad3 and TTF-1/NKX2-1 complex regulates Smad4-independent gene expression.
No sample metadata fields
View SamplesNIH3T3 in the middle of G0 to G1 transion consists of the cells which is still staying G0 phase and the cells which enters G1. Monitoring the expressions of p27 and Cdt1 enables to distinguish these two; p27+/Cdt1+ cells as the cells in G0 phase and p27-Cdt1+ cells as G1 phase
A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.
Cell line
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