GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE161961 Query DataSets for GSE161961
Status Public on Apr 23, 2021
Title Hltf-deletion from the TME in a CDX model of CRC reprogrammed the human transcriptome-S-nitroso-proteome to promote inflammation and redirect metastasis
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hypermethylation of helicase-like transcription factor (HLTF) in colorectal cancer (CRC) cells occurs more frequently in men than women. Progressive epigenetic silencing of HLTF in tumor cells is accompanied by negligible expression in the tumor microenvironment (TME). Cell line-derived xenografts were established in control (Hltf+/+) and Hltf-deleted male Rag2-/-IL2rg-/- mice by direct orthotopic microinjection of HLTF+/+HCT116 cells into the submucosa of the cecum. Combinatorial induction of IL6 and S100A8/A9 in the Hltf-deleted TME with ICAM-1 and IL8 in the primary tumor activated a positive feedback loop. The proinflammatory niche produced a major shift in CDX metastasis to peritoneal dissemination compared to controls. Inducible nitric oxide (iNOS) gene expression and transactivation of the iNOS-S100A8/A9 signaling complex in Hltf-deleted TME reprogrammed the human S-nitroso-proteome. S-nitroso (SNO) proteins POTEE, TRIM52 and UN45B are S-nitrosylated on the conserved I/L-X-C-X2-D/E motif indicative of iNOS-S100A8/A9-mediated S-nitrosylation. 2D-DIGE and protein identification by MALDI-TOF/TOF mass spectrometry authenticated S-nitrosylation of 53 individual cysteines in half-site motifs (I/L-X-C or C-X-X-D/E) in CDX tumors. POTEE-SNO in CDX tumors is both a general S-nitrosylation target and an iNOS-S100A8/A9 site-specific (Cys638) target in the Hltf-deleted TME. REL is an example of convergence of transcriptomic-S-nitroso-proteomic signaling. The gene is transcriptionally activated in CDX tumors with an Hltf-deleted TME, and REL-SNO (Cys143) is found in primary CDX tumors and all metastatic sites. Primary CDX tumors from Hltf-deleted TME shared 60% of their S-nitroso-proteome with all metastatic sites. Forty percent of SNO-proteins from primary CDX tumors were variably expressed at metastatic sites. Global S-nitrosylation of proteins in pathways related to cytoskeleton and motility is strongly implicated in the metastatic dissemination of CDX tumors. Hltf-deletion from the TME plays a major role in the pathogenesis of inflammation and links protein S-nitrosylation in primary CDX tumors with spatiotemporal continuity in metastatic progression even when the tumor cells express HLTF.
Overall design HCT116 cells that express HLTF were paced in mice that either do (control) or do not (test) express the Hltf gene. Resultant, primary CDX tumors were excised, profiled with RNAseq, and subjected to species specific mapping, Comparisons of gene expresison profiles for tumors (human) and the tumor microenvironment (mouse) were generated.
Web link
Contributor(s) Helmer RA, Martinez-Zaguilan R, Kaur G, Smith LA, Dufour JM, Chilton BS
Citation(s) 34010296, 37682902
Submission date Nov 22, 2020
Last update date Sep 13, 2023
Contact name Beverly S Chilton
Phone 806-743-2709
Organization name Texas Tech University HSC
Department Cell Biology & Biochemistry
Lab 5B136 & 137
Street address 3601 4th St-MS6540
City Lubbock
State/province TX
ZIP/Postal code 79430
Country USA
Platforms (1)
GPL22245 Illumina HiSeq 2500 (Homo sapiens; Mus musculus)
Samples (6)
GSM4928824 Index13OtC3221+cells+mice
GSM4928825 Index14OtC3222+cells+mice
GSM4928826 Index15OtC3223+cells+mice
BioProject PRJNA680156
SRA SRP293693

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE161961_RAW.tar 48.9 Mb (http)(custom) TAR (of XLSX)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap