Serine-Driven Metabolic Plasticity Drives Adaptive Resilience in Pancreatic Cancer Cells [PANC-1]
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PROVIDER: PRJNA1241820 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic cancer is one of the most lethal malignancies, partly due to its profound metabolic adaptability, which contributes to drug resistance and therapeutic failure. Understanding how pancreatic cancer cells reprogram their metabolism in response to treatment may uncover new therapeutic vulnerabilities. This study investigates the metabolic adaptations underlying resistance to drug treatment in pancreatic cancer using a systems metabolomics approach to explore novel biomarkers and therapeutic strategies. Methods: Eight human pancreatic cancer cell lines were analyzed to assess metabolic heterogeneity and drug response. Untargeted and isotope-labeled metabolomics were performed to evaluate metabolic rewiring before and after treatment with erastin, a redox-disrupting agent. Differential correlation analysis was applied to identify key metabolic nodes associated with treatment adaptation. Combinatorial treatments using FDA-approved drugs targeting glycolysis and one-carbon metabolism were tested. Multi-omics integration of metabolomics and transcriptomics data was conducted to elucidate mechanisms of resistance. Results: Pancreatic cancer cell lines exhibited marked metabolic heterogeneity, with differences in nutrient dependency and mitochondrial activity. Erastin treatment revealed metabolic vulnerabilities but failed to sustain long-term growth suppression. Combinatorial treatments of erastin with methotrexate or alpelisib significantly reduced proliferation and induced metabolic alteration. A systems-level analysis identified serine metabolism as a central adaptive pathway activated in resistant mechanism. Metabolic tracing and gene expression analyses revealed increased de novo serine biosynthesis and uptake, coupled with enhanced redox balancing and epigenetic regulation. Notably, cell lines that reactivated growth after drug withdrawal exhibited transcriptional reprogramming involving serine-driven pathways. These adaptations were associated with increased expression of survival, proliferation and migration-related genes. Conclusions: This study demonstrates that pancreatic cancer cells rewire their metabolism in response to combinatorial drug treatment by activating serine synthesis and uptake. These metabolic adaptations sustain redox homeostasis, biosynthetic processes and transcriptional reprogramming, contributing to resistance mechanism. Serine metabolism emerges as a functional biomarker of metabolic plasticity and drug tolerance. These insights open new avenues for metabolism-based strategies to overcome resistance and advance precision therapy in pancreatic cancer.
2025-07-08 | GSE292891 | GEO
Project description:Serine-Driven Metabolic Plasticity Drives Adaptive Resilience in Pancreatic Cancer Cells [HPAF-2]
| PRJNA1241817 | ENA
Project description:Pancreatic cancer is one of the most lethal malignancies, partly due to its profound metabolic adaptability, which contributes to drug resistance and therapeutic failure. Understanding how pancreatic cancer cells reprogram their metabolism in response to treatment may uncover new therapeutic vulnerabilities. This study investigates the metabolic adaptations underlying resistance to drug treatment in pancreatic cancer using a systems metabolomics approach to explore novel biomarkers and therapeutic strategies. Methods: Eight human pancreatic cancer cell lines were analyzed to assess metabolic heterogeneity and drug response. Untargeted and isotope-labeled metabolomics were performed to evaluate metabolic rewiring before and after treatment with erastin, a redox-disrupting agent. Differential correlation analysis was applied to identify key metabolic nodes associated with treatment adaptation. Combinatorial treatments using FDA-approved drugs targeting glycolysis and one-carbon metabolism were tested. Multi-omics integration of metabolomics and transcriptomics data was conducted to elucidate mechanisms of resistance. Results: Pancreatic cancer cell lines exhibited marked metabolic heterogeneity, with differences in nutrient dependency and mitochondrial activity. Erastin treatment revealed metabolic vulnerabilities but failed to sustain long-term growth suppression. Combinatorial treatments of erastin with methotrexate or alpelisib significantly reduced proliferation and induced metabolic alteration. A systems-level analysis identified serine metabolism as a central adaptive pathway activated in resistant mechanism. Metabolic tracing and gene expression analyses revealed increased de novo serine biosynthesis and uptake, coupled with enhanced redox balancing and epigenetic regulation. Notably, cell lines that reactivated growth after drug withdrawal exhibited transcriptional reprogramming involving serine-driven pathways. These adaptations were associated with increased expression of survival, proliferation and migration-related genes. Conclusions: This study demonstrates that pancreatic cancer cells rewire their metabolism in response to combinatorial drug treatment by activating serine synthesis and uptake. These metabolic adaptations sustain redox homeostasis, biosynthetic processes and transcriptional reprogramming, contributing to resistance mechanism. Serine metabolism emerges as a functional biomarker of metabolic plasticity and drug tolerance. These insights open new avenues for metabolism-based strategies to overcome resistance and advance precision therapy in pancreatic cancer.
2025-07-08 | GSE292890 | GEO
Project description:An adaptive stress response that confers cellular resilience to decreased ubiquitination
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Project description:The interplay between phenotypic plasticity and adaptive evolution has long been an important topic of evolutionary biology. This process is critical to our understanding of a species evolutionary potential in light of rapid climate changes. Despite recent theoretical work, empirical studies of natural populations, especially in marine invertebrates, are scarce. In this study, we investigated the relationship between adaptive divergence and plasticity by integrating genetic and phenotypic variation in Pacific oysters from its natural range in China. Genome resequencing of 371 oysters revealed unexpected fine-scale genetic structure that is largely consistent with phenotypic divergence in growth, physiology, thermal tolerance and gene expression across environmental gradient. These findings suggest that selection and local adaptation are pervasive and together with limited gene flow shape adaptive divergence. Plasticity in gene expression is positively correlated with evolved divergence, indicating that plasticity is adaptive and likely favored by selection in organisms facing dynamic environments such as oysters. Divergence in heat response and tolerance implies that the evolutionary potential to a warming climate differs among oyster populations. We suggest that trade-offs in energy allocation are important to adaptive divergence with acetylation playing a role in energy depression under thermal stress.
2018-07-27 | PXD008057 | Pride
Project description:Stress resilience is a dynamic process whereby an individual can withstand stressful events while still maintaining normal, physiological functioning. Resilience is inferred from an observed level of cognitive performance higher than expected in the face of a demonstrated stressful event. The neural rewiring that leads to stress resilience resides in structural and functional synaptic plasticity. The importance of studying stress resilience has become more evident in the last years, considering the frequency and variety of stressors that humans have to cope with and the attendant stress-related disorders, and especially now more than ever due to the COVID-19 worldwide crisis. The molecular basis for stress resilience and the factors that modulate it are important research areas in neuropsychiatry and contemporary neuroscience.
2025-05-06 | PXD026590 | Pride
Project description:Analysis of differentially expressing genes in whole genome wide analysis of aptamer SQ2 positive cells (Capan-1, Panc-1, Panc-1+ve) and SQ2 negative cells (Panc-1-ve and HPDE) Panc-1 +ve and Panc-1-ve cell lines were generated from Panc-1 cell line based upon its hetergenous binding to aptamer SQ2. Detailed procedure of generation of these cell lines are described in Pooja Dua, Hye Suk Kang, Seung-Mo Hong, Ming-Sound Tsao, Soyoun Kim, and Dong-ki Lee. 2012 Alkaline Phosphatase ALPPL2 is a novel pancreatic carcinoma-associated protein. Cancer Research A five chip study using total RNA recovered from Capan-1, Panc-1, Panc-1+ve, Panc-1-ve and HPDE cells. Each chip measures 45,033 genes with three 60 mer probe pairs per target.
2012-11-21 | E-GEOD-42428 | biostudies-arrayexpress
Project description:Adaptive plasticity of IL10 + and IL35 + regulatory T cells
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Project description:Gemcitabine has been a first-line therapeutic agent for pancreatic ductal adenocarcinoma (PDAC) pancreatic cancer; however, acquisition of resistance to gemcitabine remains a major challenge. We analyzed miRNAs expression profiles by array-based miRNAs analysis between gemcitabine–resistant (PANC-1/GEM) and parental PANC-1 cells.
2016-12-31 | GSE79234 | GEO
Project description:Analysis of differentially expressing genes in whole genome wide analysis of aptamer SQ2 positive cells (Capan-1, Panc-1, Panc-1+ve) and SQ2 negative cells (Panc-1-ve and HPDE) Panc-1 +ve and Panc-1-ve cell lines were generated from Panc-1 cell line based upon its hetergenous binding to aptamer SQ2. Detailed procedure of generation of these cell lines are described in Pooja Dua, Hye Suk Kang, Seung-Mo Hong, Ming-Sound Tsao, Soyoun Kim, and Dong-ki Lee. 2012 Alkaline Phosphatase ALPPL2 is a novel pancreatic carcinoma-associated protein. Cancer Research
2012-11-21 | GSE42428 | GEO