Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant pulmonary epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of unselected cells. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8-weeks post-selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short term assays and enhanced outgrowth of premalignant lesions in longer term assays, thus overcoming important aspects of metastatic inefficiency. Overall, our findings indicate that among premalignant pulmonary epithelial cells, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior.
Identification of a Human Airway Epithelial Cell Subpopulation with Altered Biophysical, Molecular, and Metastatic Properties.
Age, Specimen part
View SamplesComparing the mRNA expression profiles of c-Myb deficient and c-Myb sufficient Tcra-/- DP thymocytes.
c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL.
No sample metadata fields
View SamplesLeptin binding to the leptin receptor (LepR) causes rapid signaling to the nucleus. We investigated the early (2 hr) transcriptional response to acute leptin injection (intracerebroventricular)
Leptin Induces Mitosis and Activates the Canonical Wnt/β-Catenin Signaling Pathway in Neurogenic Regions of <i>Xenopus</i> Tadpole Brain.
Treatment
View SamplesMicroarray analysis was performed to determine the transcriptional profiles of NKT, CD1d-aGC+ Va24-, and CD4 T cells.
A naive-like population of human CD1d-restricted T cells expressing intermediate levels of promyelocytic leukemia zinc finger.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy.
Specimen part, Treatment
View SamplesT cell anergy is one of the mechanisms contributing to peripheral tolerance, particularly in the context of progressively growing tumors and in tolerogenic treatments promoting allograft acceptance. We recently reported that early growth response gene 2 (Egr2) is a critical transcription factor for the induction of anergy in vitro and in vivo, which was identified based on its ability to regulate the expression of inhibitory signaling molecules diacylglycerol kinase (DGK)-a and -z. We reasoned that other transcriptional targets of Egr2 might encode additional factors important for T cell anergy and immune regulation. Thus, we conducted two sets of genome-wide screens: gene expression profiling of wild type versus Egr2-deleted T cells treated under anergizing conditions, and a ChIP-Seq analysis to identify genes that bind Egr2 in anergic cells. Merging of these data sets revealed 49 targets that are directly regulated by Egr2. Among these are inhibitory signaling molecules previously reported to contribute to T cell anergy, but unexpectedly, also cell surface molecules and secreted factors, including lymphocyte-activation gene 3 (Lag3), Class-I-MHC-restricted T cell associated molecule (Crtam), Semaphorin 7A (Sema7A), and chemokine CCL1. These observations suggest that anergic T cells might not simply be functionally inert, and may have additional functional properties oriented towards other cellular components of the immune system.
Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy.
Specimen part, Treatment
View SamplesComparative analyses of Mex67 and Npl3 binding to mRNA at normal growth condition (25째C) and upon shift to heat stress (30 min, 42째C). Overall design: Examination of two biological RNA Co-IP replicates of Mex67, Npl3 and no tag control at 25째C and upon shift to 30 min at 42째C (Heat stress) and subsequent Illumina RNA deep-sequencing
mRNA quality control is bypassed for immediate export of stress-responsive transcripts.
Cell line, Subject
View SamplesTo identify genes that require PLZF for their regulation in NKT cells, we compared the developmental stages of thymic NKT cells from wildtype and PLZF-deficient mice
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Specimen part
View SamplesWe used a high-throughput technology, DNA microarray, to screen the entire genome for the changes in gene expression in diseased tissue to characterize Dupuytren's contracture at a molecular level and find genes that are involved in development of the disease.
Microarray analysis of Dupuytren's disease cells: the profibrogenic role of the TGF-β inducible p38 MAPK pathway.
Sex, Specimen part
View Samples