Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA244880 | ENA |
REPOSITORIES: ENA
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Project description:Metastasis leads to the majority of deaths in breast cancer patients. Here we investigated the molecular and biochemical signaling pathways altered by RECK, a major metastasis suppressor gene in breast cancer. We overexpressed RECK in 2 highly invasive cell lines and knocked-down RECK expression in 2 poorly invasive cell lines. IPA analysis of differentially expressed genes revealed IL-6, and IL8 signaling alteration with RECK pertubation. This lead us to discover that RECK suppresses metastasis and neoangiogenesis at secondary sites by inhibiting STAT3 dependent VEGF & uPA regulating. This finding is significant because it reveals the biology behind a major metastasis suppressor gene in cancer.
2014-09-01 | GSE56898 | GEO
Project description:Metastasis leads to the majority of deaths in breast cancer patients. Here we investigated the molecular and biochemical signaling pathways altered by RECK, a major metastasis suppressor gene in breast cancer. We overexpressed RECK in 2 highly invasive cell lines and knocked-down RECK expression in 2 poorly invasive cell lines. IPA analysis of differentially expressed genes revealed IL-6, and IL8 signaling alteration with RECK pertubation. This lead us to discover that RECK suppresses metastasis and neoangiogenesis at secondary sites by inhibiting STAT3 dependent VEGF & uPA regulating. This finding is significant because it reveals the biology behind a major metastasis suppressor gene in cancer. Cell lines were obtained from the ATCC or were generous gifts from Dr Joan Massague (MSKCC). Invasive cell lines were stably infected with a constitutively expressing RECK construct or and Empty Vector control. Poorly invasive cell lines were transfected with a Scramble siRNA or siRNA targeting the RECK gene. RNA was extracted using the RNeasy kit (Qiagen) as per the manufacturer’s instructions. Expression analysis was performed using the Affymetrics U133 2.0 microarray (Affymetrix). Affymetrix CEL files were imported into the Partek Genomics Suite (Partek).
2014-09-01 | E-GEOD-56898 | biostudies-arrayexpress
Project description:Epigenetic alterations are widely linked with carcinogenesis, therefore becoming emerging therapeutic targets in the treatment of cancers, including breast cancer. HMGNs are nucleosome binding proteins, which regulate chromatin structures in a cell type- and disease-specific manner. However, the roles of HMGNs in the tumorigenesis of breast cancer are less known. In this study, we report that HMGNs are highly expressed in 3D-cultured breast cancer cells. HMGN5, a member of HMGNs, controls the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Clinically, HMGN5 is an unfavorable prognostic marker in patients. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape oncogenic chromatin landscape and transcriptional program. Lastly, we provide evidence that interference of HMGN5 by nanoparticle-packaged siRNA is potentially an effective approach in breast cancer treatment. Taken together, our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic target in STAT3-hyperactive breast cancer.
2022-08-31 | GSE193507 | GEO
Project description:RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock- and RECK-transfected HT1080 cells. Three established cell lines were selected for RNA extraction and hybridization on Affymetrix microarrays: (1) mock-transfected HT1080 cells, designated as HT1080-Zeo, (2) RECK-overexpressing HT1080 cells, designated as HT1080-RECK, and (3) RECK/4NQ-overexpressing HT1080 cells (in which four N-glycosylation asparagine residues of RECK (Asn86, Asn200, Asn297, and Asn352) were replaced with glutamine residues), designated as HT1080-RECK/4NQ.
2010-04-14 | E-GEOD-21306 | biostudies-arrayexpress
Project description:Knock-down of ovarian cancer amplification target ADRM1 leads to down regulation of GIPC1 and up-regulation of RECK. Among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification, and was significantly upregulated with respect to stage, recurrence and metastasis. In addition, overexpression of ADRM1 correlated significantly with shorter time to recurrence and overall survival. Herein, array-CGH and microarray expression of ovarian cancer cell lines, provides evidence consistent with the primary tumor data that ADRM1 is a 20q13 amplification target. Knock-down of ADRM1 in amplified ovarian cell line OAW42 results in down-regulation of growth factor GIPC1 and up-regulation of tumor-suppressor RECK RNA and protein. In our dataset of 141 ovarian primary tumors, ADRM1 overexpression significantly correlates with GIPC1 overexpression. In addition, there is a significant anticorrelation between ADRM1 overexpression and RECK expression. Further research is necessary to determine whether targeting knock-down of ADRM1 in 20q13-amplified ovarian cancers results in growth inhibition and tumor suppression via downstream targets GIPC1 and RECK. ADRM1 siRNA treated OAW42 compared directly to untreated or nonspecific RNA treated OAW42
2011-01-14 | E-GEOD-26634 | biostudies-arrayexpress
Project description:To investigate potential links between Stat3 transcriptional activity and other signaling pathways in breast cancer, we determined the gene expression profiles of three breast cancer cell lines treated with JAK, PTGIS, PFKFB3, CXCR2, HAS1, or NQO1 inhibitor (all of which decreased Stat3 transcriptional activity in Hs 578T cells except for the NQO1 inhibitor), inhibitor treatment vehicle alone (DMSO), STAT3 siRNAs, or non-targeting siRNAs. Using the resulting data, we identified a gene signature that was significantly regulated by STAT3 siRNAs and similarly affected by the JAK and at least 3 other inhibitors (or by 4 other inhibitors) but not by the NQO1 inhibitor in Hs 578T cells that was enriched in genes involved in development and correlated with shorter distant metastasis-free survival in primary lymph-node-negative invasive breast tumors. These results emphasize the central importance of Stat3 in CD44+/CD24- stem-cell-like breast cancer cells. This study includes SAGE-Seq libraries obtained using 27 samples that each underwent individual protocols. There are nine samples of each of three cell lines - Hs 578T, MCF7, and SUM159PT. The samples in each group were treated with either one of the six inhibitors, DMSO only (the background control for inhibitor-treated cells), STAT3 siRNAs, or non-targeting siRNAs (the background control for STAT3 siRNAs).
2011-09-08 | E-GEOD-22917 | biostudies-arrayexpress
Project description:Epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) processes are proposed to be a driving force of cancer metastasis. By studying metastasis in bone marrow-derived mesenchymal stem cell (BM-MSC)-driven lung cancer models, microarray time-series data analysis by systems biology approaches revealed BM-MSC-induced signaling triggers early dissemination of CD133+/CD83+ cancer stem cells (CSCs) from primary sites shortly after STAT3 activation but promotes proliferation towards secondary sites. The switch from migration to proliferation was regulated by BM-MSC-secreted LIF and activated LIFR/p-ERK/pS727-STAT3 signaling to promote early disseminated cancer cells MET and premetastatic niche formation. Then, tumor-tropic BM-MSCs circulated to primary sites and triggered CD151+/CD38+ cells acquiring EMT-associated CSC properties through IL6R/pY705-STAT3 signaling to promote tumor initiation and were also attracted by and migrated towards the premetastatic niche. In summary, STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates the EMT-MET switch within the distinct molecular subtypes of CSCs to complete the metastatic process.
2020-10-01 | GSE158824 | GEO
Project description:We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(-) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN. 91 specimens of primary infiltrating ductal carcinoma of breast (IDC) included triple negatives(48/91), ERBB2+(29/91),ER(-)PR(+)HER(-)(5/91), ER(-)PR(+)HER(+)(6/91) and ER(-) but HER(?)(3/91). Five specimens for metaplastic carcinoma of breast (MCB) were included. Seven non-tumor samples were surgically taken from breast tissue adjacent to some of 91 ER(-) IDC breast tumors as a control in this study.
2012-09-25 | E-GEOD-32641 | biostudies-arrayexpress
Project description:Modulating Immune Cells to Prevent Breast Cancer Lung Metastasis
| PRJNA436027 | ENA
Project description:Metastasis is responsible for the majority of cancer-related deaths1. Although single-cell RNA sequencing (scRNA-seq) has revealed considerable heterogeneity among tumor cells, identifying the cellular determinants of metastasis has remained challenging. Here, we analyzed scRNA-seq data of primary human breast tumor biopsies and identified a minority population of immature THY1+/VEGFA+ basal epithelial cells that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher levels of LMO2+ basal cells in human breast tumors correlated with endothelial content and predicted poor distant recurrence-free survival. Using MMTV-PyMT/Lmo2CreERT2 mice, we demonstrate that Lmo2 lineage-traced cells integrate into the vasculature and metastasize to the lung. In human breast tumors, knockdown of LMO2 reduced lung metastasis by affecting multiple steps required for intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 is a binding partner of STAT3 and is required for STAT3 activation in the presence of the inflammatory cytokines, TNFα and IL6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis.
2023-10-08 | GSE159284 | GEO