Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1314137 | ENA |
REPOSITORIES: ENA
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Project description:Comparson of Biphenotypic hepatocytes with Mature Hepatocytes Biphenotypic hepatocytes were isolated from DDC-injured liver as Sox9+EpCAM- cells. Gene expression profile of biphenotypic hepatocytes were compared with that of Mature hepatocytes.
2016-03-02 | E-GEOD-78778 | biostudies-arrayexpress
Project description:Comparson of Biphenotypic hepatocytes with Mature Hepatocytes
2016-03-02 | GSE78778 | GEO
Project description:Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative malignancy caused by clonal expansion of granular lymphocytes. Two subgroups, (cytotoxic) T-cell LGLL and natural killer (NK) cell LGLL, are defined based on their cellular origin and expression of characteristic surface molecules. In this study, we performed a comparative proteome profiling of isolated extracellular vesicles (EV) from the T-LGLL cell line MOTN-1 and the NK-LGLL line NKL.
2024-10-17 | PXD053228 | Pride
Project description:Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy characterized by human T-cell leukemia virus type 1 (HTLV-1) infection. ATL has a very poor prognosis and lacks satisfactory treatments; therefore, it is critical to identify novel targets in ATL cells in order to develop effective targeted therapeutics. Here we report the identification of two novel oncogenes, AK4 and RHOC, as target genes of miR-455-3p, a tumor suppressive microRNA in ATL patients. Importantly, AK4 and RHOC are highly expressed in ATL and exhibit oncogenic potentials in vitro and in vivo. Interestingly, transcriptome and metabolome analyses reveal a functional overlap of AK4 and RHOC, including activating oncogenic pathways such as Myc targets and deregulating lipid metabolism such as enhancing the production of sphingomyelin, a tumor-promoting lipid. In particular, compared to other types of T-cell malignancy such as T-ALL and CTCL, ATL is sensitive to sphingomyelin inhibition and AK4 or RHOC depletion. Altogether, we report a distinct dependency of ATL on newly characterized oncogenes AK4 and RHOC and an oncometabolite sphingomyelin, which together represent novel targetable vulnerabilities of ATL that could be exploited for developing effective therapeutics.
2025-02-03 | MTBLS11858 | MetaboLights
Project description:Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy characterized by human T-cell leukemia virus type 1 (HTLV-1) infection. ATL has a very poor prognosis and lacks satisfactory treatments; therefore, it is critical to identify novel targets in ATL cells in order to develop effective targeted therapeutics. Here we report the identification of two novel oncogenes, AK4 and RHOC, as target genes of miR-455-3p, a tumor suppressive microRNA in ATL patients. Importantly, AK4 and RHOC are highly expressed in ATL and exhibit oncogenic potentials in vitro and in vivo. Interestingly, transcriptome and metabolome analyses reveal a functional overlap of AK4 and RHOC, including activating oncogenic pathways such as Myc targets and deregulating lipid metabolism such as enhancing the production of sphingomyelin, a tumor-promoting lipid. In particular, compared to other types of T-cell malignancy such as T-ALL and CTCL, ATL is sensitive to sphingomyelin inhibition and AK4 or RHOC depletion. Altogether, we report a distinct dependency of ATL on newly characterized oncogenes AK4 and RHOC and an oncometabolite sphingomyelin, which together represent novel targetable vulnerabilities of ATL that could be exploited for developing effective therapeutics.
2025-02-03 | MTBLS11844 | MetaboLights
Project description:The oncogenic proteins expressed in human cancer cells are exceedingly difficult targets for drug discovery due to intrinsic properties of the Ras GTPase switch. As a result, recent efforts have largely focused on inhibiting Ras-regulated kinase effector cascades, particularly the Raf/MEK/ERK and PI3 kinase/Akt/mTOR pathways. We constructed murine stem cell leukemia virus (MSCV) vectors encoding oncogenic K-RasD12 with additional “second site” amino acid substitutions that that impair PI3 kinase/Akt or Raf/MEK/ERK activation and performed bone marrow transduction/transplantation experiments in mice. In spite of attenuated signaling properties, defective K-Ras oncoproteins induced aggressive clonal T lineage acute lymphoblastic leukemia (T-ALL). These leukemias exhibited a high frequency of somatic Notch1 mutations, which is also true of human T-ALL. Multiple independent T-ALLs restored full oncogenic Ras activity by acquiring “third site” mutations within the viral KrasD12 transgenes. Other leukemias with undetectable PTEN and elevated phosphoryated Akt levels showed a similar gene expression profile to human early T progenitor (ETP) T-ALL. Expressing oncoproteins that are defective for specific functions is a general strategy for assessing requirements for tumor maintenance and uncovering potential mechanisms of drug resistance in vivo. In addition, our observation that defective Kras oncogenes regain potent cancer initiating activity strongly supports simultaneously targeting distinct components of Ras signaling networks in the substantial fraction of cancers with RAS mutations. WT Balb/c mice were lethally irradiated and transplanted with WT Balb/c bone marrow cells transduced with MSCV-IRES-Kras mutant-GFP vectors. Mice developed T-cell lymphoproliferative disease.
2011-09-30 | E-GEOD-28687 | biostudies-arrayexpress
Project description:To identify targets of aberrantly expressed RTK-fusion oncogenes, serine/threonine and tyrosine phosphorylation signatures in transgenic cells lines expressing different RTK-fusion oncogenes were compared with their respective kinasedead mutant counterparts. Comparing the differentially phosphorylated proteins between the different RTK fusions were used to identify commonly deregulated pathways as well as pathways specifically targeted by individual RTK-fusions.
2026-01-22 | PXD059984 | Pride
Project description:Multiple myeloma (MM) evolves from highly prevalent premalignant condition termed Monoclonal Gammopathy of Undetermined Significance (MGUS). We report an MGUS-MM phenotype arising in transgenic mice with Emu-directed expression of the unfolded protein/ER stress response and plasma cell development spliced isoform factor XBP-1s. Emu-XBP-1s elicited elevated serum Ig and IL-6 levels, skin alterations and with advancing age, a significant proportion of Emu-xbp-1s transgenic mice develop features diagnostic of human MM including bone lytic lesions. Transcriptional profiles of Emu-xbp-1s B lymphoid and MM cells show aberrant expression of genes known to be dysregulated in human MM including Cyclin D1, MAF, MAFB, and APRIL. This genetic model coupled with documented frequent XBP-1s overexpression in human MM serve to implicate chronic XBP-1s dysregulation in the development of this common and lethal malignancy. Experiment Overall Design: In this study, we have explored the biological impact of sustained XBP-1s expression in the lymphoid system, anticipating that this genetic event would be a necessary component along with other MM-relevant oncogenes and tumor suppressor gene manipulations to generate a MM-prone mouse model. Unexpectedly, XBP-1s overexpression alone yielded an MGUS-MM disease bearing many features classical of the human disease on the clinical, pathological and molecular levels. Experiment Overall Design: We performed expression analysis of B cells derived from the spleen of 20-week old Emu-xbp-1s mice (n=5) and non-transgenic mice (n=5). Additionally, we analyzed the expression profiles from MM tumor cells arising in Emu-xbp-1s mice (n=6).
2007-11-06 | E-GEOD-6980 | biostudies-arrayexpress
Project description:Despite their long half-life, therapeutic antibodies are considered ineffective against intracellular antigens due to their perceived inability to penetrate epithelial cells. Using recombinant antibodies targeting common mutations in oncogenes, we show that dimeric IgA, but not the same antibody on an IgG backbone, penetrates human epithelial cancer cells through PIGR-dependent directional transcytosis, specifically neutralizing mutated oncodrivers and expelling antigens outside the cell, bound to secretory IgA. Accordingly, targeting of KRasG12D or IDH1R132H with antigen-specific dimeric IgA abrogated the growth of different carcinomas in a mutation-specific manner, including in syngeneic tumor-bearing immunocompetent mice. Our results provide a rationale for developing PIGR-targeting tumor cell-penetrating antibodies to effectively target common mutations in intracellular oncogenes that drive many aggressive and frequent human cancers.
2025-05-06 | PXD042914 | Pride
Project description:Cancers induced by human papillomaviruses should, in principle, be responsive to immunotherapy by virtue of expressing the immunogenic oncoproteins E6/E7 that drive malignancy. Rather, advanced forms of cervical cancer are poorly responsive to immune response-enhancing treatments involving therapeutic vaccination against these viral neo-antigens. Leveraging a transgenic mouse model for HPV-derived cancers, termed K14HPV16/H2b, we demonstrate that therapeutic vaccination with a nanoparticle-based vaccine alone or in combination with anti-PD-1/anti-CTLA4 does not elicit tumor regression nor increase the minimal CD8+ T cell infiltrates in the tumor microenvironment (TME), suggesting the presence of immunosuppressive barriers. We demonstrated that myeloid cells in lymphoid organs of K14HPV16/H2b mice possess potent immunosuppressive activity for both antigen presenting cells and CD8+ T cells that dampens the anti-tumor immune responsiveness. Our data highlight a link between HPV-induced cancers, systemic amplification of myeloid cells, and the detrimental effects of these cells on the generation of anti-tumor immune responses in the periphery, resulting in poor CD8 T cell activation and limited migration to the tumor site.
2020-09-16 | GSE126913 | GEO