Project description:In bladder, loss of mammalian Sonic Hedgehog (Shh) accompanies progression to invasive urothelial carcinoma, but the molecular mechanisms underlying this cancer-initiating event are poorly defined. Here, we show that loss of Shh results from hypermethylation of the CpG shore of the Shh gene, and that inhibition of DNA methylation increases Shh expression to halt the initiation of murine urothelial carcinoma at the early stage of progression. In full-fledged tumors, pharmacologic augmentation of Hedgehog (Hh) pathway activity impedes tumor growth, and this cancer-restraining effect of Hh signaling is mediated by the stromal response to Shh signals, which stimulates subtype conversion of basal to luminal-like urothelial carcinoma. Our findings thus provide a basis to develop subtype-specific strategies for the management of human bladder cancer.
Project description:RNA-seq analysis was performed on TICs and the parental counterparts of 4 LSCC cell lines. In addition, PRKCI knock down (KD) variants of these cells were sequenced. Subsequent analysis revealed that activation of HH signaling, a known driver of the TIC phenotype, is dependent on PRKCI expression. Examination of TICS, parental cells, parental PRKCI KD cells, and TIC PRKCI KD cells
Project description:In this study, we provide evidence that spheroids cells isolated from established human NSCLC cell lines are highly enriched in NSCLC-TICs that aberrant Akt-IL6-Stat3 signalling axis is necessary for self-renewal of lung TICs in vitro and for tumor formation in vivo.
Project description:RNA-seq analysis was performed on TICs and the parental counterparts of 4 LSCC cell lines. In addition, PRKCI knock down (KD) variants of these cells were sequenced. Subsequent analysis revealed that activation of HH signaling, a known driver of the TIC phenotype, is dependent on PRKCI expression.
Project description:Hedgehog (Hh) proteins are morphogens which regulate embryonic development and adult tissue homeostasis, with distinct outcomes dependent on the strength and duration of their signals. We show that the Hh signalling pathway modulates the induction and pathology of mouse atopic dermatitis. Sonic hedgehog (Shh) and Hh pathway target genes were upregulated on induction of atopic dermatitis, and the Hh pathway was activated in skin T cells, showing that they respond in vivo to Hh signals secreted from the skin. Shh upregulation reduced skin inflammation in mice, whereas pharmacological Smoothened-inhibition reduced Shh upregulation and exacerbated skin pathology. Hh-signalling to T cells prevented skin inflammation on induction of dermatitis, while inhibition of Hh-mediated transcription in T cells substantially exacerbated the disease. RNA-sequencing analysis of skin CD4+ T cells from mice with chronic atopic dermatitis revealed decreased expression of immune regulatory genes in mice with conditional inhibition of Hh-mediated transcription in T cells, and increased expression of inflammatory and chemokine genes. In contrast, constitutive Hh mediated transcription in T cells led to increased expression of immune regulatory genes in skin CD4+ T cells from mice with chronic atopic dermatitis and protected against inflammation. Hh-mediated transcription in T cells resulted in increased regulatory T (Treg) cells in the periphery and skin of dermatitis-induced mice, and increased TGF-β expression, supporting their immunoregulatory phenotype, whereas, inhibition of T cell specific Hh-mediated transcription, resulted in impaired Treg function, which permitted progression of skin inflammation.
Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (pancreatic cancer, esophageal cancer, tongue squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and lung squamous cell carcinoma) were subjected to Agilent whole genome microarrays.
Project description:Using H3K27ac ChIP-seq profile to map active enhancers in lung cancer and endometrial carcinoma cells ChIP-seq of H3K27ac was done in lung adenocarcinoma cell lines (NCI-H358 and NCI-H2009), squamous cell lung carcinoma cell lines (HCC95) and endometrial carcinoma cell lines (Ishikawa)
Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (lung squamous cell carcinoma, oral squamous cell carcinoma, renal cell carcinoma and prostate cancer) were subjected to Agilent whole genome microarrays.
Project description:Despite similarities between tumor initiating cells with stem-like properties (TICs) and normal neural stem cells, we hypothesized that there may be differences in their differentiation potentials. We now demonstrate that both bone morphogenetic protein (BMP)-mediated and ciliary neurotrophic factor (CNTF)-mediated Jak/STAT-dependent astroglial differentiation is impaired due to EZH2-dependent epigenetic silencing of BMP receptor 1B (BMPR1B) in a subset of glioblastoma TICs. Forced expression of BMPR1B either by transgene expression or demethylation of the promoter restores their differentiation capabilities and induces loss of their tumorigenicity. We propose that deregulation of the BMP developmental pathway in a subset of glioblastoma TICs contributes to their tumorigenicity both by desensitizing TICs to normal differentiation cues, and by converting otherwise cytostatic signals to pro-proliferative signals. Experiment Overall Design: DNA extracted from four glioma cell lines were hybridized to 50K mapping arrays (Xba only) to detect and summarize chromosomal aberrations in those samples.
Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (bladder cancer, prostate cancer, renal cell carcinoma, oral squamous cell carcinoma and lung squamous cell carcinoma) were subjected to Agilent whole genome microarrays.
