D122p53 mice (a model of D133p53 isoform) are tumour prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed 122p53 mice with IL-6 deficient mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence, and metastasis. We also show that D122p53 activates RhoA-ROCK signalling leading to tumour cell invasion which is IL-6 dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that 133p53 activates the these pathways, resulting in invasive and migratory phenotypes, in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with D133TP53 mRNA. Patients with elevated D133TP53 mRNA levels had a shorter disease free survival. Our results suggest that D133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways and that patients whose tumours have high D133p53 may benefit from therapies targeting these pathways.
∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling.
Specimen part
View SamplesThe TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.
Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy.
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ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.
Sex, Specimen part
View SamplesElf5 expression in mammary progenitor cells regulates a cell fate decision that establishes the alveolar cell lineage. In luminal breast cancer cells, increased Elf5 expression suppressed estrogen receptor and FoxA1 expression and was implicated in the acquisition of resistance to the cytostatic effects of antiestrogen therapy. We show that in the PyMT model of luminal breast cancer, increased Elf5 expression drives lung metastasis by recruiting myeloid-derived suppressor cells, and that this activity overcomes the epithelializing influence of Elf5. Breast cancer expression signatures identify a similar process in humans, and increased Elf5 immunohistochemical staining predicts poor prognosis in the luminal A subgroup. Thus Elf5 may promote escape from hormonal therapy and drive metastasis in luminal breast cancer.
ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.
Sex, Specimen part
View SamplesElf5 expression in mammary progenitor cells regulates a cell fate decision that establishes the alveolar cell lineage. In luminal breast cancer cells, increased Elf5 expression suppressed estrogen receptor and FoxA1 expression and was implicated in the acquisition of resistance to the cytostatic effects of antiestrogen therapy. We show that in the PyMT model of luminal breast cancer, increased Elf5 expression drives lung metastasis by recruiting myeloid-derived suppressor cells, and that this activity overcomes the epithelializing influence of Elf5. Breast cancer expression signatures identify a similar process in humans, and increased Elf5 immunohistochemical staining predicts poor prognosis in the luminal A subgroup. Thus Elf5 may promote escape from hormonal therapy and drive metastasis in luminal breast cancer.
ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells.
Sex, Specimen part
View SamplesAnalysis of the gene signature of OX40+ Tregs, in comparison to OX40- Tregs and Tconvs, freshly isolated from liver cirrhosis and tumor of chronic HCV patients.
Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth.
Specimen part
View SamplesAn unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sex, Specimen part
View SamplesFoxo1 is required for proper developmental progression due to distinct functions at different stages of B cell development, but specific gene targets in pro-B cells are not identified. We performed a microarray analysis in v-Abl transformed pro-B cells to compare the gene expression pattern between wildtype and Foxo1 knockout cells.
MK5 activates Rag transcription via Foxo1 in developing B cells.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Sex, Specimen part, Time
View SamplescDNA and cRNA hybridization technologies have different, probe-specific sensitivities. We used samples from an etanercept trial (GSE11903) to explore in a real-life setting the uniqueness of each platform.
Cross-study homogeneity of psoriasis gene expression in skin across a large expression range.
Specimen part, Time
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