Project description:To analyze the effects of Cdh1 signaling on melanoma properties, we performed microarray analysis to identify genes induced by soluble Cdh1 in mouse melanoma cell line B16-F10.
Project description:To futher understand the properties of CDH1+ GSCs and CDH1- GSCs, flow cytometry was used to sort the twopopulations after trypsin digestion and they were compared by total RNA sequencing (RNA-seq). The data clearlyshowed CDH1+ and CDH1- cells as having highly distinct profiles. In particular, numerous epithelial genes (e.g.Dsp, Pkp2, Krt19) were highly expressed in the CDH1+ population. In contrast, most genes known to be generalmarkers of SSCs/undifferentiated spermatogonia were downregulated (e.g. GFRA1 and ID4) or unchanged (e.g. ZBTB16and SALL4) in CDH1- GSCs. Additionally, KEGG pathway analysis revealed that the two populations exhibiteddistinctive activity in several signaling pathways including WNT and TGFb signaling. Notably, Tgfbr1, Smad2, Smad3tended to be lower in CDH1+ GSCs while Smad7, an inhibitor of TGFb signaling, was higher.The results showed thatCDH1+ GSCs were more epithelial in nature compared to CDH1- GSCs and supported the notion that CDH1+ GSCs are areable to partly overcome MET barrier because they may be in an advanced stage of MET.
Project description:Objective was to uncover the transcriptional changes occuring in melanoma-associated LECs relative to LECs of naïve skin. To investigate the transcriptional changes in LECs during tumor development, RNA was extracted from LECs sorted from naïve skin and BPC (Tyr::Cre-ER, BRafV600E) murine melanomas and bulk RNA-seq performed. Naïve skin LECs were collected from 3 mice and tumor-associated LECs collected from 4 mice.
Project description:Employing Cre/loxP technology, a mouse model of liver specific Cdh1 (E-cadherin) depletion was created (fl/fl | +/wt). Previously, the mice had already been compared to littermates with normal Ecadherin levels (fl/fl | wt/wt), using a broad range of laboratory methods (Serum parameters, long-term weight analysis, histology, western blot, etc.). To analyze the effect of Cdh1 (E-Cadherin) depletion on the liver homeostasis on the RNA-level over the course of 3 time-points, liver tissue was aquired from mice groups aged 1 week, 3 weeks and 6 weeks. Mice with liver-specific Cdh1 depletion were compared to wildtype-like littermates. 1 week: n=2+2; 3 weeks: n=3+3; 6 weeks: n=3+3. Samples (mice) were not paired.
Project description:Employing Cre/loxP technology, a mouse model of liver specific Cdh1 (E-cadherin) depletion was created (fl/fl | +/wt). Previously, the mice had already been compared to littermates with normal Ecadherin levels (fl/fl | wt/wt), using a broad range of laboratory methods (Serum parameters, long-term weight analysis, histology, western blot, etc.). To analyze the effect of Cdh1 (E-Cadherin) depletion on the liver homeostasis on the RNA-level over the course of 3 time-points, liver tissue was aquired from mice groups aged 1 week, 3 weeks and 6 weeks.
Project description:In this study, we wanted to explore the protein interactors of Cdh1, a subunit of the E3 Ubiquitin-Ligase Cdh1-APC. Our data show that in addition to interacting with other components of the Cdh1-APC complex, Cdh1 interacts with regulators of translation.
Project description:Expression profiles of 17 melanoma cell lines were analysed to identify genes differentially expressed between cell lines harbouring wild-type or mutant p16INK4A. Relevant paper: Pavey et al. (2007). Note: all of these cell lines contained wild-type p14ARF, so that the transcriptional effects of p16INk4A could be determined without interference from p14ARF. Experiment Overall Design: The aim of this study was to identify genes which are transcriptional targets of p16INK4A in melanoma.
Project description:We conducted transcriptome analysis usin next generation sequencing of paired WT or CDH1 KO hGO cells established from three patients' fundic gands. Compared to WT hGOs, CDH1 KO hGO cells showed higher expression of matrix metalloproteinase (MMP) genes and genes that regulate inflammation and angiogenesis. We showed that the migration ability of CDH1 KO hGO cells was mediated by upregulation of MMPs and this effect was abolished by specific inhibitor of MMPs in vitro. MMP-3 protein was expressed in clinical samples of E-cadherin deficient signet ring cell carcinoma (SRCC) of the stomach. Our study represents that MMPs are promising candidates for novel therapeutic targets for E-cadherin-deficient SRCC.
Project description:Because TP53 mutation and CDH1 inactivation are the most common abnormalities found in human type II endometrial carcinomas, the contribution of dysfunctional TRP53 and CDH1 in the tumor microenvironment to induce type II endometrial cancer was characterized using mouse as a model. The results of our analysis revealed that conditional deletion of Cdh1 and Trp53 in the uterus regulated most of the genes categorized by their involvement in inflammatory responses, immune cell trafficking, cellular movement, cell-to-cell signaling and interaction and cellular growth and proliferation. A direct comparison of mouse uteri (n=3) from control, single ablation of Cdh1 or Trp53, and ablation of both Cdh1 and Trp53 at 2 months of age.