Targeting a Galectin-3/EGR1 transcriptional complex inhibits the pro-metastatic signature in TRIM49-deficient gastric adenocarcinoma II
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE291323 | GEO | 2025/09/17
REPOSITORIES: GEO
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Project description:Distal metastasis, driven by intracellular signaling rewiring, is a leading cause of cancer mortality. The role of post-translational modifications in metastasis remains unclear. A CRISPR screen in a gastric adenocarcinoma (GAC) mouse model identified TRIM49 as a metastasis suppressor. TRIM49 is downregulated in most advanced GACs, correlating with poor prognosis. Galectin-3, stabilized in TRIM49-deficient cells due to impaired degradation, forms a complex with EGR1, enhancing pro-metastatic gene expression. Disrupting this complex with GB1107 inhibits metastasis in mouse models. The Galectin-3/EGR1 complex in TRIM49-deficient GAC is a key driver of metastasis and a potential therapeutic target.
2025-09-17 | GSE289465 | GEO
Project description:The biocontrol agent Pseudomonas chlororaphis PA23 protects canola (Brassica napus) against infection by the necrotrophic fungus Sclerotinia sclerotiorum. Production of PA23 secondary metabolites is governed by a complex regulatory pathway that includes the GacA/GacS two component system, the PhzI/PhzR quorum-sensing system, and a novel LysR-type transcriptional regulator, called PtrA. Through RNA-sequencing, transcriptomic profiles of PA23-WT, two quorum sensing-deficient strains, PA23-AHL and PA23-phzR, and regulatory mutants PA23-gacA, PA23-gacS and PA23-ptrA were generated allowing elucidation of the PhzRI, Gac and PtrA regulons of P. chlororaphis PA23.
2018-05-26 | GSE114924 | GEO
Project description:Prostate cancer (PCa) causes significant mortality among men worldwide. Galectin-4 plays an important roles in regulatiog cancer metastasis and high level of galectin-4 correlated with poor survival in subpopulation of PCa patients. To further understand the galectin-4-mediated signature and develop effective treatment, we froced expressed galectin-4 in 22Rv1 and LNCaP cells, and downregulated galectin-4 in 22Rv1-M4 cells. Next, cDNA microarray were applyed to study galectin-4-mediated gene expression and cancer progression.
2018-06-30 | GSE100301 | GEO
Project description:Hyperactive angiogenesis contributes to the immunosuppressive microenvironment important for immunotherapy, and LGALS1-encoed galectin-1 can trigger vascular signaling programs and mediate anti-angiogenic treatment response. However, the mechanism of galectin-1 regulation of angiogenesis is poorly understood. Previous mRNA interactome studies suggested that galectin-1 associated with mRNAs. In this study, we applied the iRIP-seq methodology, an unbiased genome-wide approach to study the RNA binding profiles of galectin-1. The results demonstrate that galectin-1 interacted with a large population of mRNAs with a preferred location towards stop codon, and preferred motifs of UGCA/UGGA and GAGCAG motifs. Galectin-1-bound mRNAs are enriched in cell cycle control and diverse basic biological processes, including its previously reported protein targets H-Ras and also T cell receptors TLR6. Glectin-1 significantly binds to genes in angiogenesis, which included the key pro-angiogenic growth factor VEGFA, angiogenic regulators EGR1 and LAMA5, suggesting that galectin-1 may regulate via its mRNA binding activity. The presented results uncover an previously unrecognized mRNA binding activity of galectin-1; further pursue of this activity could lead to knowledge important for developing therapeutic strategies against cancer and other diseases involved in aberrant angiogenesis.
2021-10-14 | GSE147565 | GEO
Project description:Understanding how the tumor microenvironment (TME) is orchestrated along the continuum of gastric adenocarcinoma (GAC) may uncover novel therapeutic strategies. Here, we performed comprehensive single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and phenotypes during tumorigenesis and progression. IgA+ plasma cells appear to be the most active regulators in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominated the late-stage GACs. We discover six TME ecotypes, four of which are unique to the premalignant/progression in the continuum, with two ecotypes, identified in primary GACs, showing strong associations with histopathologic, genomic characteristics and prognosis. Extensive stromal remodeling is evident with GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) correlates with aggressive phenotypes and poor survival and SDC2 overexpression in CAFs contributes to tumor growth. This study illustrates a roadmap of the GAC TME and highlights potential targets for further investigation.
2023-06-10 | GSE234129 | GEO
Project description:Although galectin-3 is known to modulate the cell proliferation, RNA processing, tumorigenesis, metastasis and apoptosis and also, which is highly expressed in human cancers, the function of galectin-3 is still controversy in gastric cancer. Here, we demonstrated the function of galectin-3 on gastric cancers by silencing with synthetic double-stranded small interfering RNA (siRNA). After silencing of galectin-3, cell numbers decreased and cell shapes changed in round. To determine the mechanism, microarray analysis was used to detect the changes in gene expression by galectin-3 silencing. we silenced galectin-3 in AGS as a gastric cancer cells with synthetic double-stranded small interfering RNA (siRNA), and performed the microarray analysis to detect the changes in gene expression by galectin-3 silencing.
2011-05-31 | E-GEOD-29630 | biostudies-arrayexpress
Project description:Although galectin-3 is known to modulate the cell proliferation, RNA processing, tumorigenesis, metastasis and apoptosis and also, which is highly expressed in human cancers, the function of galectin-3 is still controversy in gastric cancer. Here, we demonstrated the function of galectin-3 on gastric cancers by silencing with synthetic double-stranded small interfering RNA (siRNA). After silencing of galectin-3, cell numbers decreased and cell shapes changed in round. To determine the mechanism, microarray analysis was used to detect the changes in gene expression by galectin-3 silencing.
2011-05-31 | GSE29630 | GEO
Project description:The functions of EGR1, a multifunctional transcription factor, in prostate cancer are well documented. However, little is known about the functions of EGR1 in lung cancer. we observed the function of EGR1 in non-small cell lung carcinoma (NSCLC) and identified the genes that influence cell fate and tumor development. We used microarrays to detail the global programme of gene expression and identified genes differentially expressed when EGR1-overexpressed. We have demonstrated that EGR1 is able to increase cell apoptosis, and inhibit metastasis. And we sought to find genes distributed to decrease the malignancy of human non-small cell lung cancer regulated by EGR1. To that end, H1299 cells were transfected either EGR1 or pcDNA3.1. After 48h, cells were collected for RNA extraction and hybridization on Affymetrix microarrays (PEGR1 VS PCDNA3.1).
2013-09-17 | E-GEOD-50913 | biostudies-arrayexpress
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response. 3 different experimental groups were studied. Galectin-3 WT CD8 T cells adoptively transferred into Galectin-3 WT mice, galectin-3 WT CD8 T cells transferred into galectin-3 KO mice, and finally galectin-3 KO CD8 T cells transferred into galectin-3 KO mice. Galectin-3 WT CD8 T cells transferred into Galectin-3 WT mice were used as the reference group. Four biological replicates were submitted for each group, and adoptively transfered CD8 T cells were isolated 5 days post-adoptive transfer into tumor-bearing mice treated with a whole cell GM-CSF secreting vaccine. Cells were purified by cell sorting on the Thy1.2 surface marker.
2015-02-19 | E-GEOD-59454 | biostudies-arrayexpress
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response.
2015-02-19 | GSE59454 | GEO