Gene expression profiles of Dclk1+ and Dclk1- PDAC cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139167 | GEO | 2020/10/20
REPOSITORIES: GEO
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Project description:Gene expression profiles of Dclk1+ and Dclk1- PDAC cells
| PRJNA578683 | ENA
Project description:Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We leveraged chemoproteomic profiling and structure-based design to develop the first selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool to investigate DCLK1 biology and establish its role in cancer.
2020-04-06 | GSE140490 | GEO
Project description:Dclk1 (Doublecortin like kinase-1) labels a rare population of long-lived and largely quiescent cells in the adult mouse pancreas. The expression of Dclk1+ vs Dclk1- pancreatic cells (mostly acinar) is observed.
2016-04-11 | GSE74429 | GEO
Project description:Doublecortin-like kinase 1 (DCLK1) is a putative cancer stem cell marker, a promising diagnostic and prognostic maker for malignant tumors and a proposed driver gene for gastric cancer. Here we show that DCLK1 expression in the gastric cancer cell line MKN1 impacts EV biogenesis both quantitatively and qualitatively in a kinase dependent manner, revealing a hitherto unknown role for this putative oncogenic kinase. Importantly, the proteome of EVs isolated from DCLK1 expressing gastric cancer cells is enriched for proteins involved in tumor-promoting biological processes, raising the prospect of establishing DCLK1 as a novel anti-cancer target.
2021-03-23 | PXD021371 | Pride
Project description:Accumulating evidence has shown the existence of tumor stem cells, and many researchers and clinicians are focusing on the therapeutic potential of targeting tumor stem cells. Previously, we reported that doublecortin like kinase 1 (Dclk1) marks tumor stem cells but not normal stem cells in ApcMin/+ mouse intestine, and that selective ablation of Dclk1+ cells results in collapse of the intestinal tumors without any apparent damages in the normal mucosa. Here, we sought to clarify gene expresion profile of Dclk1+ cells by microarray analyses in mouse normal intestinal epithelium and ApcMin/+ mouse intestinal tumors. Microarray analyses demonstrated that genes related to microtubules and actin cytoskeleton (e.g., Rac2) were highly expressed in Dclk1+ normal intestinal and tumor cells. We found the expression of Src family kinases (i.e., Hck, Lyn, Csk, and Ptpn6) in Dclk1+ normal intestinal and tumor cells.
2017-06-05 | GSE99387 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53-/- mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN-signaling.
2020-10-15 | GSE134092 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most metastatic cancers in human. PDACs respond poorly to therapies, partly due to cancer stem cells (CSCs) that self-renew, survive chemotherapies, metastasise and replenish the tumor. Factors secreted by tumor cells mediate autocrine/paracrine crosstalk with surrounding cells contributing to the stem cell niche but are still insufficiently characterised. Here we used quantitative SILAC proteomics to identify secreted factors enriched in CSC secretome compared to non-CSCs. Our data uncovered factors that mediate the crosstalk between CSCs and non-CSCs as well as genes mediating the gene expression circuitries regulating CSC proliferation.
2024-02-18 | GSE244326 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest and most metastatic cancers in human. PDACs respond poorly to therapies, partly due to cancer stem cells (CSCs) that self-renew, survive chemotherapies, metastasise and replenish the tumor. Factors secreted by tumor cells mediate autocrine/paracrine crosstalk with surrounding cells contributing to the stem cell niche but are still insufficiently characterised. Here we used quantitative SILAC proteomics to identify secreted factors enriched in CSC secretome compared to non-CSCs. Our data uncovered factors that mediate the crosstalk between CSCs and non-CSCs as well as genes mediating the gene expression circuitries regulating CSC proliferation.
2024-02-18 | GSE244287 | GEO
Project description:Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis and human cancers. However, the role of DCLK1 in atherosclerosis remains undefined. In this study, we identified up-regulated DCLK1 in macrophages in atherosclerotic lesions of ApoE-/- mice fed an HFD and determined that macrophage-specific DCLK1 deletion attenuates atherosclerosis by reducing inflammation in mice. Mechanistically, RNA sequencing analysis indicated that DCLK1 mediates oxLDL-induced inflammation via NF-κB signaling pathway in primary macrophages. Co-immunoprecipitation followed by LC-MS/MS analysis identified IKKβ as a binding protein of DCLK1. We confirmed that DCLK1 directly interacts with IKKβ and phosphorylates IKKβ at S177/181, thereby facilitating subsequent NF-κB activation and inflammatory gene expression in macrophages. Finally, a pharmacological inhibitor of DCLK1 prevents atherosclerotic progression and inflammation both in vitro and in vivo. Our findings demonstrated that macrophage DCLK1 promotes inflammatory atherosclerosis by binding to IKKβ and activating IKKβ/NF-κB. This study reports DCLK1 as a new IKKβ regulator in inflammation and a potential therapeutic target for inflammatory atherosclerosis.
2022-12-24 | GSE221647 | GEO
Project description:Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis and human cancers. However, the role of DCLK1 in atherosclerosis remains undefined. In this study, we identified up-regulated DCLK1 in macrophages in atherosclerotic lesions of ApoE-/- mice fed an HFD and determined that macrophage-specific DCLK1 deletion attenuates atherosclerosis by reducing inflammation in mice. Mechanistically, RNA sequencing analysis indicated that DCLK1 mediates oxLDL-induced inflammation via NF-κB signaling pathway in primary macrophages. Co-immunoprecipitation followed by LC-MS/MS analysis identified IKKβ as a binding protein of DCLK1. We confirmed that DCLK1 directly interacts with IKKβ and phosphorylates IKKβ at S177/181, thereby facilitating subsequent NF-κB activation and inflammatory gene expression in macrophages. Finally, a pharmacological inhibitor of DCLK1 prevents atherosclerotic progression and inflammation both in vitro and in vivo. Our findings demonstrated that macrophage DCLK1 promotes inflammatory atherosclerosis by binding to IKKβ and activating IKKβ/NF-κB. This study reports DCLK1 as a new IKKβ regulator in inflammation and a potential therapeutic target for inflammatory atherosclerosis.
2023-02-27 | PXD039083 | Pride