Project description:The purpose of this study was to assess the preliminary antitumor activity, safety and tolerability of tepotinib in combination with cetuximab in participants with RAS/BRAF wild-type left-sided Metastatic Colorectal Cancer (mCRC) having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.
Project description:This SuperSeries is composed of the following subset Series: GSE12811: CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer (expr) GSE12813: CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer (aCGH) Refer to individual Series
Project description:Genomic analysis was performed to distinguish expression changes in murine medial edge epithelial cells during both palatal adherence and epithelial-mesenchymal transformation (EMT). Assessment of changes between sample 0 hours and sample 12 hours represent palatal adherence. Changes between sample 12 hours and sample 24 hours represent EMT. During adherence, we found that genes necessary for TGF-beta/LEF-1 signal transduction upregulate, as well as those necessary for cell adhesion. During EMT, we observed the loss of epithelial markers and upregulation of many genes necessary to promote the transition to mesenchyme and cell migration.
Project description:Oncogenic transformation alters the metabolism of cellular lipids to sustain tumor growth. We define a reciprocal mechanism by which cholesterol metabolism controls the formation and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of Nsdhl, or treatment with cholesterol-lowering statins caused murine pancreatic carcinomas induced by KrasG12D expression and homozygous Trp53 loss to undergo a differentiation switch from a glandular to basal (mesenchymal) phenotype. In parallel, PDACs from patients receiving statins had enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induced sterol response element binding protein 1 (SREBP1), promoting autocrine transforming growth factor beta (TGF) signaling, inducing epithelial-mesenchymal transition. Activation of promesenchymal TGFβ effectors by cholesterol-lowering statins may select for poorly differentiated carcinomas.
Project description:Epithelial-Mesenchymal Transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. Following Snail-1 induction, epithelial markers were repressed within 6 hours and mesenchymal genes induced at 24 hours. Snail-1 binding to its target promoters was transient (6-48 hours) despite continued protein expression and it was followed by both transient and long-lasting chromatin changes.
Project description:Epithelial-Mesenchymal Transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. Following Snail-1 induction, epithelial markers were repressed within 6 hours and mesenchymal genes induced at 24 hours. Snail-1 binding to its target promoters was transient (6-48 hours) despite continued protein expression and it was followed by both transient and long-lasting chromatin changes.
Project description:Human epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies. In our model system, mouse bladder and kidney epithelial cells spontaneously immortalize, transform and become tumorigenic after prolonged culture. We assessed genome and transcriptome alterations and found wide-spread aneuploidy, early transcriptional deregulation, and massive genomic dereguation of the cellular transcriptome. The results reveal a remarkable similarity with genome and transcriptome aberrations detected in human tumorigenesis, hence validating our newly derived cancer models. Epithelial cells were isolated from the C57BL/6 mouse bladder and kidney. These cells underwent spontaneous transformation in culture. We sought to identify the molecuar genomic alterations that occur during the transformation process and to compare these with the changes observed in human bladder and kidney cancers.
Project description:Human epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies. In our model system, mouse bladder and kidney epithelial cells spontaneously immortalize, transform and become tumorigenic after prolonged culture. We assessed genome and transcriptome alterations and found wide-spread aneuploidy, early transcriptional deregulation, and massive genomic dereguation of the cellular transcriptome. The results reveal a remarkable similarity with genome and transcriptome aberrations detected in human tumorigenesis, hence validating our newly derived cancer models. Epithelial cells were isolated from the C57BL/6 mouse bladder and kidney. These cells underwent spontaneous transformation in culture. We sought to identify the molecuar genomic alterations that occur during the transformation process and to compare these with the changes observed in human bladder and kidney cancers.
