Project description:SOX2 is a transcription factor essential for self-renewal and pluripotency of embryonic stem cells. Recently SOX2 was found overexpressed in the majority of the lung squamous cell carcinoma (SQC), in which it acts as a lineage-survival oncogene. However, downstream targets/pathways of SOX2 in lung SQC cells remain to be identified. In order to identify genes/pathways likely to be downstream of SOX2, we conducted SOX2 silencing experiments in LK2 and NCI-H520 (H520 thereafter), two SOX2-abundant lung SQC cell lines and analyzed global gene transcription changes by gene expression microarray assay. Each of H520 and LK2 cell lines was treated with either pooled siRNAs of SOX2 or non-silencing (control) siRNAs. After 48 h, cells were harvested and totoal RNA extracted for gene expression microarray analysis using Illumina HumanHT12 v3 BeadChip.
Project description:SOX2 is a transcription factor essential for self-renewal and pluripotency of embryonic stem cells. Recently SOX2 was found overexpressed in the majority of the lung squamous cell carcinoma (SQC), in which it acts as a lineage-survival oncogene. However, downstream targets/pathways of SOX2 in lung SQC cells remain to be identified. In order to identify genes/pathways likely to be downstream of SOX2, we conducted SOX2 silencing experiments in LK2 and NCI-H520 (H520 thereafter), two SOX2-abundant lung SQC cell lines and analyzed global gene transcription changes by gene expression microarray assay.
Project description:This SuperSeries is composed of the following subset Series: GSE14859: ArrayCGH mapping of chromosome 3 aberrations in lung Squamous Cell Carcinoma (SCC) GSE14883: SOX2 overexpression effect on human lung squamous cells GSE15079: ArrayCGH mapping of the recurrent 3q26.3-q27mplifications in lung Squamous Cell Carcinoma (SCC) Refer to individual Series
Project description:SOX2 is a lineage specifier oncogene for lung squamous cell carcinoma (LSCC) and frequently amplified and overexpressed in human LSCC tumors (up to 90% of the cases). Our study demonstrated that SOX2 is a key determinant of neutrophil recruitment to tumors even in the absence of squamous histology. We generated cell lines from KrasLSL-G12D/+;Trp53fl/fl (KP) tumors that overexpress Sox2 (i.e. tumors from Lenti-Sox2-Cre infected KP mice that are validated to have Sox2 overexpression) (abbreviated as KPS) and employed chromatin immunoprecipitation sequencing (ChIP-seq) to identify genomic binding loci of SOX2 in KPS lines as well as Lkb1fl/fl;Ptenfl/fl (LP) LSCC tumors.
Project description:We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells). Human lung squamous BEAS-2B cells were transduced for Control or SOX2 expression, and their transcriptomes compared using Affymetrix arrays.
Project description:We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells).
Project description:SOX2 is a transcription factor essential for pluripotent stem cells, and development and maintenance of squamous epithelium. We previously reported SOX2 an oncogene subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here we demonstrate in SCCs that SOX2 interacts with another master squamous transcription factor p63, and through ChIP-seq show that genomic occupancy of SOX2 overlaps with that of p63 at a large number of loci and that they cooperatively regulate gene expression including ETV4, which we find essential for SOX2-amplified SCC cell survival. Furthermore, SOX2 binds to distinct genomic loci in SCCs than in embryonic stem cells and the SOX2-p63 coordinate binding is unique to SCC. In addition, a subset of SOX2 genomic binding sites in SCC that lack p63 co-occupancy are co-occupied by the AP-1 transcriptional complex. These demonstrate that SOX2’s actions in SCC differ substantially from its role in pluripotency and identify novel SOX2 interactions that will enable deeper characterization of SOX2’s function in SCC. SOX2 and p63 ChIP-seq from three lung and esophageal squamous carcinoma cell lines with amplification of SOX2 as well as SOX2 ChIP-seq from an ES cells.
Project description:Genetically engineered mouse models (GEMM) of cancer are powerful tools to study multiple aspects of caner biology. We developed a novel GEMM for lung squamous cell carcinoma (LSCC) by genetically combining overexpression of Sox2 with loss of Lkb1: Rosa26LSL-Sox2-IRES-GFP;Lkb1fl/fl (SL). We compared gene expression profiles of SL lung tumors with normal mouse lung tissue, mouse lung adenocarcinoma (LADC) tumors from KrasLSL-G12D/+;Trp53fl/fl (KP), mouse LSCC tumors from Lkb1fl/fl;Ptenfl/fl (LP) model as well as Lenti-Sox2-Cre Lkb1fl/fl.
Project description:BCL11A is upregulated in lung squamous cell carcinoma (LUSC) but not in lung adenocarcinoma (LUAD). BCL11A interacts with SOX2 at protein level. ChIP-Seq experiment was performed for BCL11A and SOX2 in LUSC LK-2 control or BCL11A-KD cell line in order to identify their role in LUSC pathology.
