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GSE51212
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We were interested in characterizing the transcriptional changes that occur on a genome-wide scale following treatment of EGFR-mutant lung cancer cells with targeted therapies.
Publication Title
Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
miRNA abnormalities are increasingly relevent to cancer development, We used microarrays to detail the global programme of gene expression upon miR-483 overexpression in sarcoma cell line MHH-ES-1.
Publication Title
The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 254 Downloadable Samples
Illumina HiSeq 2000
Description
Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: Primary tumors were established by direct prostate inoculation into immunosuppressed NSG mice of CE1-4 prostate cancer cells, derived from tissue-specific inactivation of PTEN [Pubmed ID: 20631921]. These cells, which were GFP-luciferase tagged, are noteworthy in that they have preserved expression of the androgen receptor and epithelial markers and recapitulate biological features of human prostate cancer. Six weeks following intra-prostate inoculation, multiple single DTCs were identified microscopically within the lungs (394 cells/hpf), with a smaller number in liver (54 cells/hpf), brain (9 cells/hpf) and bone marrow (1 cell/hpf). To undertake RNA sequencing of single cells during progression from quiescent DTCs to proliferative lesions, we identified GFP-tagged single tumor cells from lung harvested at various intervals, analyzing these separately from microdissected multicellular lesions. Individual DTCs collected at 6-7 weeks (DTC-I; N=20) and at 9-11 weeks (DTC-II; N=55) were compared with single cells derived from the primary tumor (N=29), lung micro-metastases (N=33), and CTCs isolated by microfluidic capture from blood specimens (N=12) [Pubmed ID: 28181495].
Publication Title
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: We performed RNA-seq on the human dermal fibroblast cell line DF treated for six hours with PGE-2 or untreated.
Publication Title
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Tumor-stromal communication within the microenvironment contributes to initiation of metastasis and may present a therapeutic opportunity. Using serial single cell RNA-sequencing in an orthotopic mouse prostate cancer model, we find upregulation of Prolactin receptor as cancer cells that have disseminated to the lung expand into micrometastases. Secretion of the ligand Prolactin by adjacent lung stromal cells is induced by tumor cell production of the COX-2 synthetic product prostaglandin E-2 (PGE-2). PGE-2 treatment of fibroblasts activates the nuclear orphan receptor NR4A (Nur77), with Prolactin as a major transcriptional target for the NR4A-Retinoid X receptor (RXR) heterodimer. Ectopic expression of Prolactin receptor in mouse cancer cells enhances micrometastasis, while treatment with the COX-2 inhibitor Celecoxib abrogates Prolactin secretion by fibroblasts and reduces tumor initiation. Across multiple human cancers, COX-2, Prolactin, and Prolactin receptor show consistent differential expression in tumor and stromal compartments. Such paracrine crosstalk may thus contribute to the documented efficacy of COX-2 inhibitors in cancer suppression. Overall design: We performed RNA-seq on the mouse prostate cancer cell line CE1-4 treated for six hours with PGE-2 or untreated.
Publication Title
COX-2 mediates tumor-stromal prolactin signaling to initiate tumorigenesis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- NextSeq 500
Description
EMT, Epithelial to mesenchymal transition is a developmental biology process associated with migration, known to be involved in cancer metastasis. To study this process, we used the breast epithelial cell line MCF10A that enter in EMT after treatment with the cytokine TGFB or by expression of EMT transcriptor factor SNAIL. Overall design: mRNA profiles of MCF10A cells treated for 1 or 6 days with TGFb (done in duplicate), and mRNA profiles of Snail inducible line, MCF10A-SNAIl, induced for 1 or 6 days.
Publication Title
Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We conducted an in vivo genome-wide CRISPR activation screen to identify genes that accelerate distal metastasis by breast cancer patient-derived circulating tumor cells (CTCs) following direct intravascular inoculation in mice. Regulators of translation and ribosomal proteins were prominent among these, and expression of RPL15, a component of the large ribosome subunit, was sufficient to increase metastatic growth in multiple organs. RPL15 overexpression selectively increases translation of other ribosomal proteins and cell cycle regulators. Unsupervised analysis of single-cell RNA sequencing of freshly-isolated CTCs from breast cancer patients identifies a subset with strong ribosomal and protein translation signatures, correlated with increased proliferative markers, epithelial markers and poor clinical outcome. Thus, ribosome protein expression identifies an aggressive subset of CTCs, whose therapeutic targeting may suppress metastatic progression.
Publication Title
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus, Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Quiescence (G0) is a transient, cell cycle-arrested state. By entering G0, cancer cells survive unfavorable conditions such as chemotherapy and cause relapse. While G0 cells have been studied at the transcriptome level, how post-transcriptional regulation contributes to their chemoresistance remains unknown. We induced chemoresistant and quiescent (G0) leukemic cells by serum-starvation or chemotherapy treatment. To study post-transcriptional regulation in G0 leukemic cells, we systematically analyzed their transcriptome, translatome, and proteome. We find that our resistant G0 cells recapitulate gene expression profiles of in vivo chemoresistant leukemic and G0 models. In G0 cells, canonical translation initiation is inhibited; yet we find that inflammatory genes are highly translated, indicating alternative post-transcriptional regulation. Importantly, AU-rich elements (AREs) are significantly enriched in the up-regulated G0 translatome and transcriptome. Mechanistically, we find the stress-responsive p38 MAPK-MK2 signaling pathway stabilizes ARE mRNAs by phosphorylation and inactivation of mRNA decay factor, tristetraprolin (TTP) in G0. This permits expression of ARE mRNAs that promote chemoresistance. Conversely, inhibition of TTP phosphorylation by p38 MAPK inhibitors and non-phosphorylatable TTP mutant decreases ARE-bearing TNFα and DUSP1 mRNAs and sensitizes leukemic cells to chemotherapy. Furthermore, co-inhibiting p38 MAPK and TNFα—prior to or along with chemotherapy—substantially reduced chemoresistance in primary leukemic cells ex vivo and in vivo. These studies uncover post-transcriptional regulation underlying chemoresistance in leukemia. Our data reveal the p38 MAPK-MK2-TTP axis as a key regulator of expression of ARE bearing mRNAs that promote chemoresistance. By disrupting this pathway, we developed an effective combination therapy against chemosurvival.
Publication Title
A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.
Sample Metadata Fields
Cell line, Treatment
View Samples