MTC and mTN cells
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ABSTRACT:
PROVIDER: PRJNA526677 | ENA |
REPOSITORIES: ENA
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Project description:RNA sequencing of mTC and mTN cells
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Project description:The goal of the study is to define the impact of long-term administration of antioxidants on lung cancer progression. mTC and mTN cell lines were established from mice with KrasG12D/+ lung tumors 58 weeks post intranasal Cre-delivery. mTC cells comes from control mice, mTN cells come from NAC-treated mice. Mice were maintained on a mixed C57BL/6-129/Sv genetic background
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Project description:Medullary thyroid cancer (MTC) accounts for less than 5% of all thyroid cancers, and it is a rare neuroendocrine tumor which derives from calcitonin-secreting thyroid C cells.Given the underlying mechanism involved in MTC remain unclear, the development and the specific pathways of MTC require further investigation.here we employed the application of TMT6plex-based LC-MS/MS to identify and analyze the novel differentially-expressed proteins(DEPs) from MTC patients, To our best knowledge, it is the first study to comprehensively investigate the molecular mechanisms of MTC by proteomics technology from Chinese MTC patients’ tissues, and these DEPs identified in our study will provide a better understanding of the underlying pathophysiology of MTC, as well as may provide potential therapeutic targets for patients with MTC.
2020-05-26 | PXD005898 | Pride
Project description:During metastasis, cancer cells travel the circulation to colonise distant sites. Due to the rarity of these events, the immediate cell fate decisions of metastasising tumour cells (mTC) are poorly understood and the role of the endothelium, as dissemination interface, remains elusive. Using a novel combinatorial mTC enrichment approach, we provide a first transcriptional blueprint of the early colonisation process
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Project description:Metastatic medullary thyroid cancer (MTC) is a currently incurable disease. FDA approved therapies that target RET, a commonly mutated receptor tyrosine kinase in MTC, and other receptor tyrosine kinases, do not result in complete responses and acquired resistance is universal due to “gatekeeper” mutation in Ret or overactivation of alternative signaling pathways. Based on data from human MTCs and a number of murine models, the CDK/RB cell cycle pathway is a potential alternative target for MTC. The objective of this study was to determine if CDKs represent therapeutic targets for MTC and to define mechanisms of activity. We demonstrate that targeting the CDK/RB pathway with Palbociclib (CDK4/6 inhibitor) is not cytotoxic to MTC cells but that Dinaciclib (CDK1/2/5/9 inhibitor) remarkably reduced cell viability and proliferation at low doses in two MTC cell lines accompanied by loss of CDK9 and RET protein and mRNA levels. In human tumors, CDK9 protein was highly expressed and array CGH demonstrated copy number gain in 11/30 analyzed tumors. RNA sequencing demonstrated that RNA polymerase II-dependent transcription was markedly reduced by Dinaciclib, consistent with transcriptional mode of action. Subsequent studies using the CDK7 inhibitor, THZ1, demonstrated high potency vs. the MTC cell lines and marked loss of RET mRNA and protein. In silico analysis, and CHIP-Sequencing using H3K27Ac antibody confirmed that RET is associated with a super-enhancer in RET-mutated MTC cells. In summary, this study reveals a novel mechanism of RET transcription regulation that represents a potentially translatable finding for new therapeutic approaches for RET-mutated MTC.
2018-12-25 | GSE114068 | GEO
Project description:N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/drosophila/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis but was known to comprise three proteins, of which two were conserved in mammals. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian orthologs. Nonetheless, the yeast MTC is arranged differently from its mammalian counterpart. The yeast MTC features a mostly mutually stabilizing core comprising Ime4/Mum2/Vir1 and the mRNA binding component Kar4, and an auxiliary hub comprising Slz1/Dyn2. The MTC core subunits when in a complex have both m6A-dependent and m6A-independent functions in meiosis. Kar4 also has a mechanistically separate function from the MTC during mating. Our findings expand the relevance of yeast as a model for unravelling m6A-dependent and independent functions of MTCs.
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Project description:ChIP sequencing of BACH1 in mTC and mTN cells
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2010-07-09 | E-GEOD-21114 | biostudies-arrayexpress
Project description:During metastasis, cancer cells travel the circulation to colonise distant sites. Due to the rarity of these events, the immediate cell fate decisions of metastasising tumour cells (mTC) are poorly understood and the role of the endothelium, as dissemination interface, remains elusive. Using a novel combinatorial mTC enrichment approach, we provide a first transcriptional blueprint of the early colonisation process
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Project description:The goal of the study is to define the impact of long-term administration of antioxidants on lung cancer progression. mTC and mTN cell lines were established from mice with KrasG12D/+ lung tumors 58 weeks post intranasal Cre-delivery. mTC cells comes from control mice, mTN cells come from NAC-treated mice. Mice were maintained on a mixed C57BL/6-129/Sv genetic background
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