Zebrafish macrophage stimulating protein (Msp) mutants compared to wild types at 3 and 6 dpf
Ontology highlight
ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE33414 | GEO | 2012/07/17
SECONDARY ACCESSION(S): PRJNA148945
REPOSITORIES: GEO
Similar Datasets
Project description:This microarray was performed in attempt to find (novel) related genes in the msp/ron signaling pathway during embryonic development Embryos from mutant versus wild type crosses were raised in standard E3 medium at 28 degrees Celcius. At 3 dpf and 6 dpf total RNA from (n=30) msp mutant versus wild type embryos was isolated using the Rnaesy mini kit (Qiagen) according to the manufactures protocol.
2012-07-16 | E-GEOD-33414 | biostudies-arrayexpress
Project description:Pancreatic cancer is an aggressive disease with a poor prognosis for which current standard chemotherapeutic treatment options offer little survival benefit. In recent years, receptor tyrosine kinases (RTK)s have garnered interest as therapeutic targets to augment or replace standard chemotherapeutic therapies because of their high expression levels in various cancers and their ability to promote cell growth, migration, and survival. Met and Ron, which are homologous RTKs activated by the ligands hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), respectively, are over-activated in many of the least treatable cancers. In pancreatic adenocarcinoma, Met expression is linked to poor patient survival and Ron expression is generally higher in tumor samples relative to normal tissue, although its prognostic significance in pancreatic cancer remains unclear. Despite the structural homology between Met and Ron, studies that have directly compared the functional outcomes of these systems in any context are limited. To address this, we sought to determine if the HGF/Met and MSP/Ron systems produce overlapping or divergent contributions towards a malignant phenotype by performing a characterization of MSP and HGF driven signaling, behavioral, and transcriptomic responses in pancreatic cancer cells in vitro. We found HGF and MSP both encouraged cell migration and activated the MAPK/Erk pathway both at the transcript and protein level. HGF uniquely increased proliferation in addition to regulating a wider variety of transcripts compared to MSP. Although HGF and MSP produced a differing breadth of responses, overlapping pro-cancer signaling, behavioral, and transcriptional effects suggest dual inhibition of the MSP/Ron and HGF/Met systems in pancreatic cancer may provide a more complete anti-cancer effect compared to individually targeting either system.
2019-06-14 | GSE129075 | GEO
Project description:Ron (Mst1r), the receptor for MSP is highly expressed in colonic epithelial cells, especially in immature cell types, such as stem cells, TA cells and immature enterocytes. To identify genes that can be induced by MSP in mouse colonic epithelial cells, we performed bulk RNA-seq using day2 colon spheroids.
2023-10-26 | GSE235733 | GEO
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers using a set of specific genes that are regulated by RON/MSP through MBD4-directed aberrant DNA methylation revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent prevents activation of the RON/MBD4 pathway and blocks metastasis of patient-derived breast tumor grafts in vivo.
2014-01-02 | GSE52688 | GEO
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers using a set of specific genes that are regulated by RON/MSP through MBD4-directed aberrant DNA methylation revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent prevents activation of the RON/MBD4 pathway and blocks metastasis of patient-derived breast tumor grafts in vivo.
2014-01-02 | GSE52687 | GEO
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent blocks metastasis of patient-derived breast tumor grafts in vivo. To determine the molecular mechanisms by which RON/MSP drives breast cancer metastasis, we performed microarray gene expression profiling of MCF7, MCF7-RON/MSP and MCF7-RON/MSP-shMBD4 cells.
2014-01-02 | E-GEOD-52567 | biostudies-arrayexpress
Project description:This microarray was performed in attempt to find genes that are related to the presence of entpd5 during embryonic development
2012-11-29 | GSE35737 | GEO
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent blocks metastasis of patient-derived breast tumor grafts in vivo.
2014-01-02 | GSE52567 | GEO
Project description:Metastasis is the major cause of death in cancer patients, yet the genetic/epigenetic programs that drive metastasis are poorly understood. Here, we report a novel epigenetic reprogramming pathway that is required for breast cancer metastasis. Concerted differential DNA methylation is initiated by activation of the RON receptor tyrosine kinase by its ligand, macrophage stimulating protein (MSP). Through PI3K signaling, RON/MSP promotes expression of the G:T mismatch-specific thymine glycosylase MBD4. RON/MSP and MBD4-dependent aberrant DNA methylation results in misregulation of a specific set of genes. Knockdown of MBD4 reverses methylation at these specific loci, and blocks metastasis. We also show that the MBD4 glycosylase catalytic residue is required for RON/MSP-driven metastasis. Analysis of human breast cancers using a set of specific genes that are regulated by RON/MSP through MBD4-directed aberrant DNA methylation revealed that this epigenetic program is significantly associated with poor clinical outcome. Furthermore, inhibition of Ron kinase activity with a new pharmacological agent prevents activation of the RON/MBD4 pathway and blocks metastasis of patient-derived breast tumor grafts in vivo. Examination of 3 cell types.
2014-01-02 | E-GEOD-52687 | biostudies-arrayexpress
Project description:This microarray was performed in attempt to find genes that are related to the presence of entpd5 during embryonic development Embryos were raised in standard E3 medium at 28 degrees Celcius. At 6 dpf mutant were separated from siblings by an in vivo skeletal staining (incubating embryos 5 minutes in 0.05% alizarin red in E3 medium where after they are extensively washed with E3 medium) as mutants fail to mineralize their skeleton. At 7 dpf, total RNA from (n=30) entpd5 mutants versus sibling embryos was isolated using the Rnaesy mini kit (Qiagen) according to the manufactures protocol.
2012-11-29 | E-GEOD-35737 | biostudies-arrayexpress