Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis III

ABSTRACT: The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor, we found that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic CRC biomarker. Correlating this observation, we could demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determined that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182466 | GEO | 2022/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis II

Project description:The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor, we found that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic CRC biomarker. Correlating this observation, we could demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determined that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.

2022-08-02 | GSE182465 | GEO

SILAC & LC-MSMS in total cell extracts or in the secretome of POU5F1B- vs. GFP-overexpressing SW480 cells

2022-10-14 | PXD028035 | Pride

Interactome of POU5F1B detected by LC-MSMS in HT29 and LS1034 CRC cells overexpressing POU5F1B-HA

2022-10-14 | PXD028034 | Pride

SILAC & LC-MSMS in total cell extracts or in the secretome of sh-scramble vs. shRNA3 & shRNA5 LS1034 cells

2022-10-14 | PXD028036 | Pride

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis I

Project description:Tumors occasionally express oncogenes via aberrant activation of transposable elements (TE), but a role for this process in oncogenesis was seldom demonstrated. Here, we identify expression of the hominid-restricted retrogene POU5F1B through aberrant activation of an endogenous retroviral promoter as a strong negative prognostic marker in colorectal cancer (CRC). We further determine that POU5F1B is membrane-enriched and interacts with ERBB2 and associated effectors, and fosters the proliferation and metastatic potential of CRC cells through intracellular signaling events and release of trans-acting molecules involved in cell growth, angiogenesis and cell adhesion. As POU5F1B is apparently non-essential and only lowly expressed in normal tissues, and as POU5F1B-containing TE-driven transcripts are detected in other tumors besides CRC, these data provide interesting leads for the development of cancer therapies.

2022-08-02 | GSE161083 | GEO

POU5F1 induces cellular heterogeneity in colorectal cancer

Project description:In this study, we aimed to identify CRC treatment resistance mechanisms by focusing on POU5F1-positive cells. Despite the small number of POU5F1-positive cells, single POU5F1-expressing cells produced heterogeneous cell populations in vitro and in vivo colorectal cancer organod. This study unveils a mechanism of CRC treatment resistance and highlights the potential of POU5F1-expressing cells as CTCs.

2023-11-29 | GSE169220 | GEO

Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues

Project description:In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions in 24 tumor and matched normal colon samples. In total, 2687 frequently hypermethylated and 468 frequently hypomethylated regions were identified, which include potential biomarkers for CRC diagnosis. Hypermethylation in the tumor samples was enriched at CpG islands and gene promoters, while hypomethylation was distributed throughout the genome. Using epigenetic data from human embryonic stem cells, we show that frequent differentially methylated regions (DMRs) coincide with bivalent loci in human embryonic stem cells. DNA methylation is commonly thought to lead to cancer gene related silencing, however integration of publically available expression analysis shows that 75% of the frequently hypermethylation genes were most likely already lowly or not expressed in normal tissue. Collectively, our study provides genome-wide DNA methylation maps of colon cancer, comprehensive lists of DMRs, and gives further clues on the role of aberrant DNA methylation in CRC formation. To investigate DNA methylation in CRC in a genome-wide unbiased fashion, we applied MethylCap-seq. This method involves capture of methylated DNA using the MBD domain of MeCP2, and subsequent next-generation Illumina sequencing of eluted DNA. In addition, we compared MethylCap with RNA-seq and ChIP-seq profiles of H3K4me3 and H3K27me3 for the colon cancer tumor cell line HCT116 (HCT116 WT) and the cell line of HCT116 with DNMT1 and DNMT3b knockout (HCT116 DKO).

2012-10-26 | E-GEOD-39068 | biostudies-arrayexpress

Functional proteomics characterization of the role of SPRYD7 in colorectal cancer progression and metastasis

Project description:SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified by spatial proteomics as upregulated in highly-metastatic to liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly-metastatic KM12C CRC cells. Here, we aimed at analyzing SPRYD7 role in CRC by functional proteomics. By immunohistochemistry, the overexpression of SPRYD7 was observed to be associated to poor survival of CRC patients, and to an aggressive and metastatic phenotype. SPRYD7 stably overexpression was performed in KM12C and SW480 poorly-metastatic CRC cells, and in their isogenic highly-metastatic to liver KM12SM and to lymph nodes SW620 CRC cells, respectively. After confirming the upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in proliferation and migration of CRC cells. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated by 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated to the stably overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated to CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance to identify novel therapeutic targets for advanced CRC.

2024-01-26 | PXD042901 | Pride

Functional proteomics characterization of the role of SPRYD7 in colorectal cancer progression and metastasis

2024-01-26 | PXD042874 | Pride

HDAC Inhibitor-Induced Acetylation of KRAS Confers A Pro-Oncogenic Effect Limiting Treatment Response in Colorectal Cancer

Project description:The limited clinical utility of HDAC inhibitors for the treatment of colorectal cancer (CRC) has until now remained an unresolved conundrum. Our findings provide comprehensive mechanistic insight into the ineffectiveness that defines HDAC inhibitors as a monotherapy for CRC. We identified that inhibition of HDAC2 promotes the emergence of a super-oncogenic KRAS by inducing K5 acetylation that fosters a previously undiscovered electrostatic interaction with R67 conserved in RAF kinases. This post-translational modification facilitates an increase in the binding affinity to this family of downstream RAS effectors, which translates into an immediate and persistent hyperactivation of the downstream MAPK-signaling. The concomitant instability of its co-conspirator c-MYC enables cells selectively harboring oncogenic KRAS to enter a protective state of reversible cell cycle arrest characterized by a senescence-like phenotype. Demonstratively, preventing this phenomenon from taking place provides a compelling alternative strategy for improving the prospects of HDAC inhibitor treatment for CRC.

2019-03-31 | GSE108191 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data