Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies Emergence of Slowly Growing Drug-Tolerant Cancer Cells
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PROVIDER: PRJNA680358 | ENA |
REPOSITORIES: ENA
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Project description:Drug resistance continues to be a major obstacle to curing cancer. Resistance can evolve from a subpopulation of cancer cells that initially survive drug treatment and then gradually form a pool of slowly growing drug-tolerant cells. Several studies have pinpointed activation of a specific bypass pathway that appears to provide the critical therapeutic target for preventing drug tolerance. Here we take a systems-biology approach using proteomics and genomics to examine the development of drug tolerance to EGFR inhibitors in EGFR-mutant lung adenocarcinoma cells and BRAF inhibitors in BRAF-mutant melanoma cells. We found that there are numerous alternative mitogenic pathways that become activated in both cases, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC) pathways. Our results suggest that an effective therapeutic strategy to prevent drug tolerance will need to take multiple alternative mitogenic pathways into account rather than focusing on one specific pathway.
2021-01-31 | GSE162045 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36626: Dynamic Deposition of the Histone H3.3 Variant Accompanies Developmental Remodeling of Arabidopsis Transcriptome (mRNA-Seq) GSE36629: Dynamic Deposition of the Histone H3.3 Variant Accompanies Developmental Remodeling of Arabidopsis Transcriptome (ChIP-Seq) Refer to individual Series
2012-05-15 | E-GEOD-36631 | biostudies-arrayexpress
Project description:Bacteria growing in biofilms are physiologically heterogeneous, due in part to their adaptation to local environmental conditions. Here, we characterized the local transcriptional responses of Pseudomonas aeruginosa growing in biofilms by using microarray analysis of isolated biofilm subpopulations. The results demonstrated that cells at the top of the biofilms had high mRNA abundances for genes involved in general metabolic functions, while mRNAs for these housekeeping genes were low in cells at the bottom of the biofilms. Selective GFP labeling showed that cells at the top of the biofilm were actively dividing. However, the dividing cells had high mRNAs levels for genes regulated by the hypoxia induced regulator, Anr. Slow-growing cells deep in the biofilms had little expression of Anr-regulated genes and may have experienced long-termanoxia. Transcripts for ribosomal proteins were primarily associated with the metabolically active cell fraction, while ribosomal RNAs were abundant throughout the biofilms, indicating that ribosomes are stably maintained even in slowly growing cells. Consistent with these results was the identification of mRNAs for ribosome hibernation factors (rmf and PA4463) at the bottom of the biofilms. A P. aeruginosa ∆rmf strain had increased uptake of the membrane integrity stain, propidium iodide. Using selective GFP labeling and cell sorting, we showed that the dividing cells were more susceptible to tobramycin and ciprofloxacin than the dormant subpopulation. The results demonstrate that in thick P. aeruginosa biofilms, cells are physiologically distinct spatially, with cells deep in the biofilm in a viable but antibiotic-tolerant slow-growth state.
2012-05-03 | GSE34762 | GEO
Project description:Bacteria growing in biofilms are physiologically heterogeneous, due in part to their adaptation to local environmental conditions. Here, we characterized the local transcriptional responses of Pseudomonas aeruginosa growing in biofilms by using microarray analysis of isolated biofilm subpopulations. The results demonstrated that cells at the top of the biofilms had high mRNA abundances for genes involved in general metabolic functions, while mRNAs for these housekeeping genes were low in cells at the bottom of the biofilms. Selective GFP labeling showed that cells at the top of the biofilm were actively dividing. However, the dividing cells had high mRNAs levels for genes regulated by the hypoxia induced regulator, Anr. Slow-growing cells deep in the biofilms had little expression of Anr-regulated genes and may have experienced long-termanoxia. Transcripts for ribosomal proteins were primarily associated with the metabolically active cell fraction, while ribosomal RNAs were abundant throughout the biofilms, indicating that ribosomes are stably maintained even in slowly growing cells. Consistent with these results was the identification of mRNAs for ribosome hibernation factors (rmf and PA4463) at the bottom of the biofilms. A P. aeruginosa M-bM-^HM-^Frmf strain had increased uptake of the membrane integrity stain, propidium iodide. Using selective GFP labeling and cell sorting, we showed that the dividing cells were more susceptible to tobramycin and ciprofloxacin than the dormant subpopulation. The results demonstrate that in thick P. aeruginosa biofilms, cells are physiologically distinct spatially, with cells deep in the biofilm in a viable but antibiotic-tolerant slow-growth state. 52-hour Pseudomonas aeruginosa TSA colony biofilms were cryoembedded, thin sectioned, and laser dissected (LCM) to obtain samples from the top and bottom 50 M-BM-5m of the biofilms. 9 sections per biofilm were pooled. RNA was extracted with the RNeasy Micro kit, Turbo DNase treated, poly(A) tailed, and amplified using the Quantitect WTA kit. After clean up, the resulting product was fragmented and end labeled before hybridization.
2012-05-02 | E-GEOD-34762 | biostudies-arrayexpress
Project description:Chemostats have been used for decades in studying cell growth under controlled environments. Whole transcriptome sequencing by RNA-seq is a relatively new method for gene expression analysis. We utilized both tools for expression analysis of Pseudomonas aeruginosa growing slowly in synthetic cystic fibrosis medium under growth-limiting nitrate and oxygen levels. We established steady-state cultures under two divergent growth rates and found that during slower growth at a doubling time of 9.8 h, 76 known quorum genes were up-expressed while just 11 were down-expressed. Quorum-controlled genes were also more expressed in response to oxygen limitation. 21% of up-expressed genes under slow, oxygen-limited growth are quorum controlled while just 6% are up-expressed under slow, nitrate-limited growth. We found that the autoinducer for regulator RhlR, C4-HSL, is ~3.4 times higher when cells are growing slowly under oxygen limitation while the concentration of the autoinducer for LasR remained unchanged. Experiments with deletion mutants show the importance of rhlR for expression of quorum-controlled genes under slow, oxygen-limited conditions. This is an intriguing observation since P. aeruginosa is likely growing in similar environments in the cystic fibrosis lung, and lasR mutations are known to arise during chronic infection.
2016-12-01 | GSE71880 | GEO
Project description:With the growing limitations on arable land, alfalfa (a widely cultivated, low-input forage) is now being selected to extend cultivation into saline lands for low-cost biofeedstock purposes. Here, minerals and transcriptome profiles were compared between two new salinity-tolerant North American alfalfa breeding populations and a more salinity-sensitive Western Canadian alfalfa population grown under hydroponic saline conditions. All three populations accumulated two-fold higher sodium in roots than shoots as a function of increased electrical conductivity. At least 50% of differentially expressed genes (p < 0.05) were down-regulated in the salt-sensitive population growing under high salinity, while remaining unchanged in the saline-tolerant populations. In particular, most reduction in transcript levels in the salt-sensitive population were observed in genes specifying cell wall structural components, lipids, secondary metabolism, auxin and ethylene hormones, development, transport, signalling, heat shock, proteolysis, pathogenesis-response, abiotic stress, RNA processing, and protein metabolism. Transcript diversity for transcription factors, protein modification, and protein degradation genes was also more strongly affected in salt-tolerant CW064027 than in salt-tolerant Bridgeview and salt-sensitive Rangelander, while both saline-tolerant populations showed more substantial up-regulation in redox-related genes and B-ZIP transcripts. The report highlights the first use of bulked genotypes as replicated samples to compare the transcriptomes of obligate out-cross breeding populations in alfalfa.
2016-07-26 | GSE84825 | GEO
Project description:With the growing limitations on arable land, alfalfa (a widely cultivated, low-input forage) is now being selected to extend cultivation into saline lands for low-cost biofeedstock purposes. Here, minerals and transcriptome profiles were compared between two new salinity-tolerant North American alfalfa breeding populations and a more salinity-sensitive Western Canadian alfalfa population grown under hydroponic saline conditions. All three populations accumulated two-fold higher sodium in roots than shoots as a function of increased electrical conductivity. At least 50% of differentially expressed genes (p < 0.05) were down-regulated in the salt-sensitive population growing under high salinity, while remaining unchanged in the saline-tolerant populations. In particular, most reduction in transcript levels in the salt-sensitive population were observed in genes specifying cell wall structural components, lipids, secondary metabolism, auxin and ethylene hormones, development, transport, signalling, heat shock, proteolysis, pathogenesis-response, abiotic stress, RNA processing, and protein metabolism. Transcript diversity for transcription factors, protein modification, and protein degradation genes was also more strongly affected in salt-tolerant CW064027 than in salt-tolerant Bridgeview and salt-sensitive Rangelander, while both saline-tolerant populations showed more substantial up-regulation in redox-related genes and B-ZIP transcripts. The report highlights the first use of bulked genotypes as replicated samples to compare the transcriptomes of obligate out-cross breeding populations in alfalfa. Three lines of Alfalfa (salt-tolerant CW064027, salt-tolerant Bridgeview, salt-sensitive Rangelander) were grown on 3 different concentrations of salt. For each cultivar-salt condition, 3 biological replicates were collected for a total of 27 samples.
2016-07-26 | E-GEOD-84825 | biostudies-arrayexpress
Project description:Over the years, many traditional rice varietites of India were sourced and studied owing to their ability to withstand abiotic pressures like excessive salinity in the soil and water. These cultivars growing in specific areas of the country represent a rich gene pool from where a deeper understanding of the processes underlying tolerance to abiotic stress can be gained. Indigenous varieties like Nonabokra and Pokkali are known salt tolerant varieties and are being studied in great detail. In the present study, we have analyzed the transcriptomes of the contrasting cultivars; Nonabokra (tolerant), Pokkali (tolerant) and IR29 (susceptible) in order to decipher the differences in their responses to salinity stress by utilizing microarray.
2021-12-31 | GSE41650 | GEO
Project description:Gene expression in tolerant and non-tolerant liver allografts
| PRJNA732295 | ENA
Project description:Heat stress along with other abiotic stresses is one of the major factors affecting crop health and overall yield in a tropical country like India. Thus, there is an urgent need to understand the dynamics of heat responsiveness at the molecular as well as physiological level. Fortunately, India has a number of indigenous varieties that show tolerance to extremes in temperature during the scorching summer months. The cultivar Annapurna is a fast growing dwarf variety of rice that is heat tolerant while the most widely grown indica rice in South and Southeast Asia, IR64, is susceptible to high temperatures. These two cultivars present an excellent opportunity to study the differences in response to heat stress, and, thereby help in elucidating the genes involved in conferring tolerance to high temperature. The present study involves transcript profiling of the two cultivars, Annapurna (tolerant) and IR64 (susceptible) under both control and heat stressed conditions.
2021-07-26 | GSE41648 | GEO