Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1200227 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31771922_1.fastq.gz | Fastqsanger.gz | |||
| SRR31771922_2.fastq.gz | Fastqsanger.gz | |||
| SRR31771923_1.fastq.gz | Fastqsanger.gz | |||
| SRR31771923_2.fastq.gz | Fastqsanger.gz | |||
| SRR31771924_1.fastq.gz | Fastqsanger.gz |
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Project description:Obesity-mediated intratumoral innervation increases pancreatic cancer tumorigenesis [scRNA-seq]
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Project description:Obesity-mediated intratumoral innervation increases pancreatic cancer tumorigenesis [Spatial Transcriptomics]
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Project description:The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, and host factors like obesity increase risk by 60% and mortality by two-fold; however, the mechanisms that drive obesity-associated tumorigenesis are poorly understood. Here, we showed that obesity-mediated pancreatic steatosis was associated with a higher level of neo-innervation in PDAC. Neo-innervation mostly comprised sympathetic neurons that released catecholamines, which ligated the adrenergic receptor on both tumor and immune cells, subsequently activating a downstream signaling cascade that led to a pro-tumorigenic type 2 immune microenvironment accelerating tumorigenesis. Further, we identified NgCAM-related cell adhesion molecule (NrCAM) and nerve growth factor (NGF) as major mediators secreted by adipocytes that drove neurogenesis. Targeting neuro-adrenergic signaling by nerve ablation or pharmacologic approaches abolished obesity-related tumor progression. Overall, this study advances our understanding of the fundamental biology underpinning obesity-mediated neo-innervation and its causal link to exacerbating PDAC development, providing new avenues for therapeutic intervention.
2026-05-08 | GSE284696 | GEO
Project description:The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, and host factors like obesity increase risk by 60% and mortality by two-fold; however, the mechanisms that drive obesity-associated tumorigenesis are poorly understood. Here, we showed that obesity-mediated pancreatic steatosis was associated with a higher level of neo-innervation in PDAC. Neo-innervation mostly comprised sympathetic neurons that released catecholamines, which ligated the adrenergic receptor on both tumor and immune cells, subsequently activating a downstream signaling cascade that led to a pro-tumorigenic type 2 immune microenvironment accelerating tumorigenesis. Further, we identified NgCAM-related cell adhesion molecule (NrCAM) and nerve growth factor (NGF) as major mediators secreted by adipocytes that drove neurogenesis. Targeting neuro-adrenergic signaling by nerve ablation or pharmacologic approaches abolished obesity-related tumor progression. Overall, this study advances our understanding of the fundamental biology underpinning obesity-mediated neo-innervation and its causal link to exacerbating PDAC development, providing new avenues for therapeutic intervention.
2026-05-08 | GSE284697 | GEO
Project description:The incidence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, and host factors like obesity increase risk by 60% and mortality by two-fold; however, the mechanisms that drive obesity-associated tumorigenesis are poorly understood. Here, we showed that obesity-mediated pancreatic steatosis was associated with a higher level of neo-innervation in PDAC. Neo-innervation mostly comprised sympathetic neurons that released catecholamines, which ligated the adrenergic receptor on both tumor and immune cells, subsequently activating a downstream signaling cascade that led to a pro-tumorigenic type 2 immune microenvironment accelerating tumorigenesis. Further, we identified NgCAM-related cell adhesion molecule (NrCAM) and nerve growth factor (NGF) as major mediators secreted by adipocytes that drove neurogenesis. Targeting neuro-adrenergic signaling by nerve ablation or pharmacologic approaches abolished obesity-related tumor progression. Overall, this study advances our understanding of the fundamental biology underpinning obesity-mediated neo-innervation and its causal link to exacerbating PDAC development, providing new avenues for therapeutic intervention.
2026-05-08 | GSE284695 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) tumors have a nutrient-poor, desmoplastic, and highly innervated tumor microenvironment. Although neurons can release stimulatory factors to accelerate PDAC tumorigenesis, the metabolic contribution of peripheral axons has not been explored. We found that peripheral axons release serine (Ser) to support the growth of exogenous Ser (exSer)-dependent PDAC cells during Ser/Gly (glycine) deprivation. Ser deprivation resulted in ribosomal stalling on two of the six Ser codons, TCC and TCT, and allowed the selective translation and secretion of nerve growth factor (NGF) by PDAC cells to promote tumor innervation. Consistent with this, exSer-dependent PDAC tumors grew slower and displayed enhanced innervation in mice on a Ser/Gly-free diet. Blockade of compensatory neuronal innervation using LOXO-101, a Trk-NGF inhibitor, further decreased PDAC tumor growth. Our data indicate that axonal-cancer metabolic crosstalk is a critical adaptation to support PDAC growth in nutrient poor environments
2025-07-07 | PXD064874 | Pride
Project description:Obesity is a major modifiable risk factor for pancreatic ductal adenocarcinoma (PDAC), yet how and when obesity contributes to PDAC progression is not well understood. Leveraging an autochthonous mouse model, we demonstrate a causal and reversible role for obesity in early PDAC progression, showing that obesity markedly enhances tumorigenesis, while genetic or dietary induction of weight loss intercepts cancer development. Bulk and single cell molecular analyses of human and murine samples define microenvironmental consequences of obesity that promote tumor development rather than new driver gene mutations. We observe increased inflammation and fibrosis and also provide evidence for significant pancreatic islet cell adaptation in obesity-associated tumors. Specifically, we identify aberrant beta islet cell expression of the peptide hormone cholecystokinin (CCK) in tumors as an adaptive response to obesity. Furthermore, islet CCK expression promotes oncogenic Kras-driven pancreatic ductal tumorigenesis. Our studies argue that PDAC progression is driven by local obesity-associated changes in the tumor microenvironment – rather than systemic effects – and implicate endocrine-exocrine signaling beyond insulin in PDAC development. Furthermore, our demonstration that these obesity-associated adaptations are reversible supports the use of anti-obesity strategies to intercept PDAC early during progression.
2020-08-12 | GSE137236 | GEO
Project description:Obesity is a major modifiable risk factor for pancreatic ductal adenocarcinoma (PDAC), yet how and when obesity contributes to PDAC progression is not well understood. Leveraging an autochthonous mouse model, we demonstrate a causal and reversible role for obesity in early PDAC progression, showing that obesity markedly enhances tumorigenesis, while genetic or dietary induction of weight loss intercepts cancer development. Bulk and single cell molecular analyses of human and murine samples define microenvironmental consequences of obesity that promote tumor development rather than new driver gene mutations. We observe increased inflammation and fibrosis and also provide evidence for significant pancreatic islet cell adaptation in obesity-associated tumors. Specifically, we identify aberrant beta islet cell expression of the peptide hormone cholecystokinin (CCK) in tumors as an adaptive response to obesity. Furthermore, islet CCK expression promotes oncogenic Kras-driven pancreatic ductal tumorigenesis. Our studies argue that PDAC progression is driven by local obesity-associated changes in the tumor microenvironment – rather than systemic effects – and implicate endocrine-exocrine signaling beyond insulin in PDAC development. Furthermore, our demonstration that these obesity-associated adaptations are reversible supports the use of anti-obesity strategies to intercept PDAC early during progression
2020-05-14 | GSE131714 | GEO
Project description:Activation of brown fat thermogenesis increases energy expenditure and alleviates obesity. Sympathetic nervous system (SNS) is important in brown/beige adipocyte thermogenesis. Here we discover a novel fat-derived “adipokine” neurotrophic factor neurotrophin 3 (NTF3) and its receptor Tropomyosin receptor kinase C (TRKC) as key regulators of SNS growth and innervation in adipose tissue. NTF3 is highly expressed in brown/beige adipocytes, and potently stimulates sympathetic neuron neurite growth. NTF3/TRKC regulates a plethora of pathways in neuronal axonal growth and elongation. Adipose tissue sympathetic innervation is significantly increased in mice with adipocyte-specific NTF3 overexpression, but profoundly reduced in mice with TRKC haploinsufficiency (TRKC+/-). Increasing NTF3 via pharmacological or genetic approach promotes beige adipocyte development, enhances cold-induced thermogenesis and protects against diet-induced obesity (DIO); whereas TRKC+/- mice or SNS TRKC deficient mice are cold intolerant and prone to DIO. Thus, NTF3 is an important fat-derived neurotrophic factor regulating SNS innervation, energy metabolism and obesity.
2021-07-15 | GSE173503 | GEO