Tiam1 methylation by NSD2 promotes Rac1 signaling activation and cancer metastasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA996217 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25337501_1.fastq.gz | Fastqsanger.gz | |||
| SRR25337501_2.fastq.gz | Fastqsanger.gz | |||
| SRR25337502_1.fastq.gz | Fastqsanger.gz | |||
| SRR25337502_2.fastq.gz | Fastqsanger.gz | |||
| SRR25337503_1.fastq.gz | Fastqsanger.gz |
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Project description:Metastasis is the key cause of failure of cancer therapy or mortality, but targeting metastatic seeding and colonization remains an unresolved challenge. Here, we report a novel molecular event in cancer metastasis mediated by NSD2/Rac1 signaling and provide a detailed mechanistic investigation of cancer metastasis. We found that NSD2, a histone methyltransferase responsible for di-methylating histone 3 at lysine 36, was overexpressed in metastatic tumors, and overexpressed NSD2 enhanced tumor metastasis both in vitro and in vivo. We further investigated that NSD2 promoted tumor metastasis by activating the Rac1 signaling pathway. Mechanistically, NSD2 methylated Tiam1, a guanine nucleotide exchange factor that facilitates GDP-Rac1 to GTP-Rac1 transition at K724. We demonstrated that Tiam1 K724 methylation plays a crucial role in Tiam1 activation and GDP-Rac1 to GTP-Rac1 transition. Specifically, we identified that Tiam1 K724 methylation could be a predictive factor in cancer prognosis, and we demonstrated that pharmacological blocking of Tiam1 K724 methylation by employing a transmembrane peptide inhibited tumor metastasis both in vitro and in vivo. Thus, NSD2-methylated Tiam1 promoted Rac1 signaling activation and cancer metastasis, which might provide novel insights into tumor metastasis inhibition.
2023-07-23 | GSE237714 | GEO
Project description:Metastasis is the key cause of failure of cancer therapy or mortality, but targeting metastatic seeding and colonization remains an unresolved challenge. Here, we report a novel molecular event in cancer metastasis mediated by NSD2/Rac1 signaling and provide a detailed mechanistic investigation of cancer metastasis. We found that NSD2, a histone methyltransferase responsible for di-methylating histone 3 at lysine 36, was overexpressed in metastatic tumors, and overexpressed NSD2 enhanced tumor metastasis both in vitro and in vivo. We further investigated that NSD2 promoted tumor metastasis by activating the Rac1 signaling pathway. Mechanistically, NSD2 methylated Tiam1, a guanine nucleotide exchange factor that facilitates GDP-Rac1 to GTP-Rac1 transition at K724. We demonstrated that Tiam1 K724 methylation plays a crucial role in Tiam1 activation and GDP-Rac1 to GTP-Rac1 transition. Specifically, we identified that Tiam1 K724 methylation could be a predictive factor in cancer prognosis, and we demonstrated that pharmacological blocking of Tiam1 K724 methylation by employing a transmembrane peptide inhibited tumor metastasis both in vitro and in vivo. Thus, NSD2-methylated Tiam1 promoted Rac1 signaling activation and cancer metastasis, which might provide novel insights into tumor metastasis inhibition.
2023-07-29 | GSE237996 | GEO
Project description:Tiam1 methylation by NSD2 promotes Rac1 signaling activation and cancer metastasis II
| PRJNA997352 | ENA
Project description:The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1. We have shown that nuclear TIAM1promotes the migration of NSCLC cells. To investigate the requirement for TIAM1 in regulating gene expression of NSCLC cells, we performed RNA-seq on H441 cells transfected with either siRNA for TIAM1 (siTIAM1) or a control siRNA (siControl) to identify differentially expressed genes.
2023-09-12 | GSE219028 | GEO
Project description:The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1. We have shown that nuclear TIAM1 promotes the migration of NSCLC cells and regulates the expression of adhesion genes as part of a repressive complex. To further investigate this, we performed ChIP-Seq analysis to determine the enrichment of TIAM1, TRIM28 and H3K9me3 to chromatin in H441 cells.
2023-09-12 | GSE219029 | GEO
Project description:We hypothesized that Tiam1 is involved in invassiveness of retinoblastoma. The fuctional role of Tiam1 in cell progression and metastasis was tested by siRNA mediated knockdown of Tiam1 in retinoblastoma Y79 cells. The genes de-regulated in response to Tiam1 knockdown was analysed by cDNA microarray in which most of the actin cytoskeleton regulation proteins and apoptotic proteins were de-regulated. our results prove that Tiam1 modulates actin cytoskeleton and cell invasion in retinoblastoma. Retinoblastoma Y79 cells were treated with Tiam1 siRNA for 48hrs and cDNA microarray was performed to analyze the genes regulated by Tiam1 silencing compared to untreated Y79 cells. Experiments were performed in triplicates.
2013-03-31 | E-GEOD-45130 | biostudies-arrayexpress
Project description:The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1 and regulates a plethora of functions such as cell proliferation, migration, apoptosis and polarity. Recently, we demonstrated that TIAM1 shuttles between the cytoplasm and nucleus. Nuclear TIAM1 has an inhibitory role on TAZ transcriptional activity by impairing the interaction of TAZ with TEAD. To further demonstrate the inhibitory role of TIAM1 on TAZ we performed ChIP-Seq analysis to determine the enrichment of TAZ to chromatin of parental or CRISPR-mediated TIAM1 knockout SW480 cells.
2017-04-26 | GSE90490 | GEO
Project description:The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1 and regulates a plethora of functions such as cell proliferation, migration, apoptosis and polarity. Recently, we demonstrated that TIAM1 shuttles between the cytoplasm and nucleus. To determine the nuclear role of TIAM1, we performed RNA-seq on SW620 cells transfected either with a specific pre-validated siRNA for TIAM1 (siTIAM1) or a negative control siRNA (siNT) and generated a list of TIAM1 differentially expressed genes. GSEA revealed significant enrichment among TIAM1-regulated genes for YAP-associated molecular signature. To investigate the interplay of TIAM1 with YAP/TAZ we used RNA-seq, generated a list of YAP/TAZ differentially expressed genes from SW620 cells transfected either with specific siRNAs for YAP/TAZ or a negative control siRNA and compared it with the siTIAM1 RNA-seq dataset. Interestingly, we found that 50% of the TAZ/YAP regulated genes were also TIAM1 dependent.
2017-04-26 | GSE90491 | GEO
Project description:We hypothesized that Tiam1 is involved in invassiveness of retinoblastoma. The fuctional role of Tiam1 in cell progression and metastasis was tested by siRNA mediated knockdown of Tiam1 in retinoblastoma Y79 cells. The genes de-regulated in response to Tiam1 knockdown was analysed by cDNA microarray in which most of the actin cytoskeleton regulation proteins and apoptotic proteins were de-regulated. our results prove that Tiam1 modulates actin cytoskeleton and cell invasion in retinoblastoma.
2013-03-31 | GSE45130 | GEO
Project description:Lung cancer is the leading cause of cancer deaths. Its high mortality is associated with high metastatic potential. Here, we show that the RAC1-selective guanine nucleotide exchange factor T cell invasion and metastasis-inducing protein 1 (TIAM1) promotes cell migration and invasion in the most common subtype of lung cancer, non-small-cell lung cancer (NSCLC), through an unexpected nuclear function. We show that TIAM1 interacts with TRIM28, a master regulator of gene expression, in the nucleus of NSCLC cells. We reveal that a TIAM1-TRIM28 complex promotes epithelial-to-mesenchymal transition, a phenotypic switch implicated in cell migration and invasion. This occurs through H3K9me3-induced silencing of protocadherins and by decreasing E-cadherin expression, thereby antagonizing cell–cell adhesion. Consistently, TIAM1 or TRIM28 depletion suppresses the migration of NSCLC cells, while migration is restored by the simultaneous depletion of protocadherins. Importantly, high nuclear TIAM1 in clinical specimens is associated with advanced-stage lung adenocarcinoma, decreased patient survival, and inversely correlates with E-cadherin expression.
2023-09-12 | GSE219030 | GEO