SOX2 is a new oncogene activated by the recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15080 | GEO | 2010/02/09
SECONDARY ACCESSION(S): PRJNA114777
REPOSITORIES: GEO
Similar Datasets
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
2010-05-14 | E-GEOD-15080 | biostudies-arrayexpress
Project description:Squamous cell carcinoma (SCC) of the lung is a frequent and aggressive cancer type. Gene amplifications, a known activating mechanism of oncogenes, target the 3q26-qter region as one of the most frequently gained/amplified genomic sites in SCC of various types. Here, we used array comparative genomic hybridization to delineate the consensus region of 3q26.3 amplifications in lung SCC. Recurrent amplifications occur in 20% of lung SCC (136 tumors in total) and map to a core region of 2 Mb (Megabases) that encompasses SOX2, a transcription factor gene. Intense SOX2 immunostaining is frequent in nuclei of lung SCC, indicating potential active transcriptional regulation by SOX2. Analyses of the transcriptome of lung SCC, SOX2-overexpressing lung epithelial cells and embryonic stem cells (ESCs) reveal that SOX2 contributes to activate ESC-like phenotypes and provide clues pertaining to the deregulated genes involved in the malignant phenotype. In cell culture experiments, overexpression of SOX2 stimulates cellular migration and anchorage-independent growth while SOX2 knockdown impairs cell growth. Finally, SOX2 over-expression in non-tumorigenic human lung bronchial epithelial cells is tumorigenic in immunocompromised mice. These results indicate that the SOX2 transcription factor, a major regulator of stem cell function, is also an oncogene and a driver gene for the recurrent 3q26.33 amplifications in lung SCC.
| S-EPMC2813300 | biostudies-literature
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. Chromosome 3 aberrations are indeed among the most frequent alterations in lung SCC and correlate with SCC patient's poor prognosis. We have precisely mapped regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC (GSE14859) amd moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. These amplicons were precisely mapped in these tumors using arraCGH with a 3q26.3 dedicated tiling array. Keywords : ArrayCGH, lung Squamous Cell Carcinoma, 3q26.3, SOX2 Keywords: ArrayCGH
2010-02-10 | GSE15079 | GEO
Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. Chromosome 3 aberrations are indeed among the most frequent alterations in lung SCC and correlate with SCC patient's poor prognosis. We have precisely mapped regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC (GSE14859) amd moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. These amplicons were precisely mapped in these tumors using arraCGH with a 3q26.3 dedicated tiling array. Keywords : ArrayCGH, lung Squamous Cell Carcinoma, 3q26.3, SOX2 Keywords: ArrayCGH Profiling of 5 advanced (stage III) lung SCC using a chromosome 3 array providing 3q26.3-q27 tiling coverage. Replicates : each array contains three replicates per clone and each sample is hybridized to two arrays, results are subsequently averaged.
2010-02-09 | E-GEOD-15079 | biostudies-arrayexpress
Project description:Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.
| S-EPMC2783775 | biostudies-literature
Project description:Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non-small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A.
| S-EPMC4742851 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-10-05 | GSE264006 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-11-25 | GSE139417 | GEO
Project description:Lung cancer causes more deaths, worldwide, than any other cancer. Several histologic subtypes exist. Currently, there is a dearth of targeted therapies for treating one of the main subtypes: squamous cell carcinoma (SCC). As for many cancers, lung SCC karyotypes are often highly anomalous owing to large somatic structural variants, some of which are seen repeatedly in lung SCC, indicating a potential causal association for genes therein. We chose to characterize a lung SCC genome to unprecedented detail and integrate our findings with the concurrently characterized transcriptome. We aimed to ascertain how somatic structural changes affected gene expression within the cell in ways that could confer a pathogenic phenotype. We sequenced the genomes of a lung SCC cell line (LUDLU-1) and its matched lymphocyte cell line (AGLCL) to more than 50x coverage. We also sequenced the transcriptomes of LUDLU-1 and a normal bronchial epithelium cell line (LIMM-NBE1), resulting in more than 600 million aligned reads per sample, including both coding and non-coding RNA (ncRNA), in a strand-directional manner. We also captured small RNA (<30 bp). We discovered significant, but weak, correlations between copy number and expression for protein-coding genes, antisense transcripts, long intergenic ncRNA, and microRNA (miRNA). We found that miRNA undergo the largest change in overall expression pattern between the normal bronchial epithelium and the tumor cell line. We found evidence of transcription across the novel genomic sequence created from six somatic structural variants. For each part of our integrated analysis, we highlight candidate genes that have undergone the largest expression changes.
| S-EPMC3514744 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer mortality worldwide, with squamous cell carcinoma (SQCC) being the second most common form. SQCCs are thought to originate in bronchial basal cells through an injury response to smoking, which results in this stem cell population committing to hyperplastic squamous rather than mucinous and ciliated fates. Copy number gains in SOX2 in the region of 3q26-28 occur in 94% of SQCCs, and appear to act both early and late in disease progression by stabilizing the initial squamous injury response in stem cells and promoting growth of invasive carcinoma. Thus, anti-SOX2 targeting strategies could help treat early and/or advanced disease. Because SOX2 itself is not readily druggable, we sought to characterize SOX2 binding partners, with the hope of identifying new strategies to indirectly interfere with SOX2 activity. We now report the first use of proximity-dependent biotin labeling (BioID) to characterize the SOX2 interactome in vivo We identified 82 high confidence SOX2-interacting partners. An interaction with the coactivator EP300 was subsequently validated in both basal cells and SQCCs, and we demonstrate that EP300 is necessary for SOX2 activity in basal cells, including for induction of the squamous fate. We also report that EP300 copy number gains are common in SQCCs and that growth of lung cancer cell lines with 3q gains, including SQCC cells, is dependent on EP300. Finally, we show that EP300 inhibitors can be combined with other targeted therapeutics to achieve more effective growth suppression. Our work supports the use of BioID to identify interacting protein partners of nondruggable oncoproteins such as SOX2, as an effective strategy to discover biologically relevant, druggable targets.
| S-EPMC5629269 | biostudies-literature