ABSTRACT: Transcriptional profiles of cultured human breast cancer cell lines treated with small molecules: 5 cell lines are treated with 109 small molecules and the expression of 978 representative genes is measured, as a part of the LINCS Joint Project.
Project description:Transcriptional profiles of multiple cell and perturbation types: 23 cells are treated with 311 chemical perturbagens and CRISPR reagents. The expression level for 978 representative genes is measured.
Project description:Transcriptional profiles of multiple cell and perturbation types: cells are treated with chemical and genetic perturbations. The expression level for 978 representative genes is measured.
Project description:Transcriptional profiles of multiple cell and perturbation types: cells are treated with chemical perturbagens and CRISPR reagents. The expression level for 978 representative genes is measured.
Project description:Transcriptional profiles of multiple cells treated with small molecule perturbagens: The expression level is measured for 978 representative genes in 15 cell lines treated with 241 small molecules.
Project description:Transcriptional profiles of cultured human cancer cell lines treated with small molecules: Expression of 978 representative genes is measured in 39 cell lines perturbed by 13 thousands of small molecules.
Project description:Transcriptional profiles of cultured human breast and prostate cancer cell lines treated with small molecules: 6 cancer cell lines are treated with 6 small molecules, as a part of the LINCS Trans-Center Project. The expression level for 978 representative genes is measured.
Project description:Thyroid carcinoma (TC) is generally associated with good prognosis, nevertheless no effective treatments are available for aggressive forms not cured by current therapies. We previously identified the coatomer protein complex zeta 1 (COPZ1), as a new putative therapeutic target for TC, since its depletion impairs the viability of tumor cells, leads to abortive autophagy, ER stress, unfolded protein response and apoptosis, and reduces the tumor growth of TC xenograft models. In this study, by combining genomic, proteomic and functional approaches, we provided evidence that COPZ1 silencing stimulates a type I IFN-mediated viral mimicry response, boosts the production of several inflammatory molecules and finally induces immunogenic cell death, which, in turn, promotes dendritic cell maturation and subsequent activation of T cells. Collectively, our findings support the notion that COPZ1 targeting can be exploited as a new strategy to kill cancer cells with the subsequent involvement of an anti-tumor immune response.
Project description:Multiple myeloma (MM) is a common hematological malignancy with poorly understood recurrence and relapse mechanisms. Notably, bortezomib resistance leading to relapse makes MM treatment significantly challenging. To clarify the drug resistance mechanism, we employed a quantitative proteomics approach to identify differentially expressed protein candidates implicated in bortezomib-resistant recurrent and relapsed MM (RRMM). Bone marrow biopsy specimens from five patients newly diagnosed with MM (NDMM) were compared with those from five patients diagnosed with bortezomib-resistant RRMM using tandem mass tag-mass spectrometry (TMT-MS). Subcellular localization and functional classification of the differentially expressed proteins were determined by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and hierarchical clustering. Top candidates identified were validated with parallel reaction monitoring (PRM) analysis using tissue samples from 11 NDMM and 8 RRMM patients, followed by comparison with the NCBI Gene Expression Omnibus (GEO) dataset of 10 MM patients and 10 healthy controls (Accession No.: GSE80608). Thirty-four differentially expressed proteins in RRMM, including proteinase inhibitor 9 (SERPINB9) were identified by TMT-MS. Subsequent functional enrichment analyses of the identified protein candidates indicated their involvement in regulating cellular metabolism, apoptosis, programmed cell death, lymphocyte-mediated immunity, and defense response pathways in RRMM. The top protein candidate SERPINB9 was confirmed by PRM analysis as well as by comparison with an NCBI GEO dataset. We elucidated the proteome landscape of bortezomib-resistant RRMM and identified SERPINB9 as a promising novel therapeutic target. Our results provide a resource for future studies on the mechanism of RRMM.
Project description:Continuous exposure to cisplatin can induce drug resistance to limit efficacy, however, the underlying mechanisms correlated to cisplatin resistance are still unclear. Drug-sensitive A549 cells and cisplatin-resistant A549/DDP cells were used to explore the potential metabolic pathways and key targets associated with cisplatin resistance by integrating untargeted metabolomics with transcriptomics. The results of comprehensive analyses showed that 19 metabolites were significantly changed in A549/DDP vs A549 cells, and some pathways had a close relationship with cisplatin resistance, such as the biosynthesis of aminoacyl-tRNA, glycerophospholipid metabolism, and glutathione metabolism. Moreover, transcriptomics analysis showed glutathione metabolism was also obviously affected in A549/DDP, which indicated that glutathione metabolism played an import role in the process of drug resistance. Meanwhile, transcriptomics analysis suggested the four enzymes related to glutathione metabolism - CD13, GPX4, RRM2B, and OPLAH - as potential targets of cisplatin resistance in NSCLC. Further studies identified the over-expressions of these four enzymes in A549/DDP. The elucidation of mechanism and discovery of new potential targets may help us have a better understanding of cisplatin resistance.