Cancer cachexia induces senescent reprogramming of brown adipose tissue and pro-cachectic S100A9 secretion by adipocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE304220 | GEO | 2026/06/25
REPOSITORIES: GEO
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| GSE304220_countMatrix.txt.gz | Txt | |||
| GSE304220_normalizedCounts.txt.gz | Txt |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:Cancer-associated cachexia (CAC) is a multifactorial, metabolic wasting syndrome that coincides with cancer malignancies of multiple entities. CAC is characterized by progressive loss of muscle mass and adipose tissue and diminishes therapy responsiveness. Here, we show that the expression of FGF21 is induced in livers of tumor-bearing mice with CAC. FGF21 deficiency promotes weight loss, exacerbates adipose tissue wasting and increases systemic inflammation, pointing towards a protective role of FGF21 in CAC. In line, IL6-mediated STAT3 activation induces FGF21 expression in hepatocytes as well as adipocytes. FGF21 promotes anabolic signaling cascades, increases cellular glucose uptake in response to IL6 exposure and counteracts cytokine-mediated glycerol release, thereby opposing adipose tissue loss in CAC. Eventually, we find that FGF21 is increased in cancer patients with clinical CAC. Together, we reveal a protective role for FGF21 in experimental CAC and identify the protein as a potential biomarker in clinical cachexia.
2025-03-06 | GSE291252 | GEO
Project description:In this study, we sought to explore the importance of selected myokines in a homogenous population of patients with gastric cancer characterized by high rates of Cancer-Associated Cachexia [CAC]. Myokine levels in peripheral blood were compared between patients with and without cachexia to identify mediators potentially involved in the pathogenesis of CAC. Moreover, we compared myokine concentrations in paired samples of portal and peripheral blood to verify whether they are released by the primary tumour. Finally, a label-free quantitative proteomics was applied to explore other potential circulating mediators of CAC and to analyse their interactions with myokines.
2025-05-06 | PXD049334 | Pride
Project description:Cancer cachexia is a multifactorial wasting syndrome affecting body and lean tissue mass that is often exacerbated by anticancer chemotherapy. In this study, we used a mouse model of acute myeloid leukemia chemotherapy induction regimen (CIR) comprising daunorubicin and cytarabine to investigate the molecular mechanisms underlying cachexia. Quantitative tandem mass tag (TMT) based proteomics was performed on skeletal muscle (quadriceps) to uncover biomarkers and pathways associated with chemotherapy induced muscle wasting. Our findings demonstrate that the AML CIR induced an acute cachexic phenotype characterized by approximately 10 percent body and lean mass loss and 20 percent muscle fibre atrophy. Through deep proteome profiling, two potential biomarkers—haptoglobin (Hp) and glutamine synthetase (Glul)—were identified. Haptoglobin in particular was responsive to cachexia severity, recovery, and exacerbation via exercise, indicating its potential as a conditionally sensitive biomarker of muscle wasting. Pathway analysis revealed upregulation of mitochondrial metabolism including branched chain amino acid catabolism and mitochondrial uncoupling proteins (Ucp1 and Ucp3), suggesting hypermetabolism as a key driver of the phenotype. These data support the use of skeletal muscle proteomics in characterizing chemotherapy induced cachexia and identifying sensitive muscle specific biomarkers for future translational and therapeutic studies.
2025-06-16 | PXD063910 | Pride
Project description:Background: Cancer cachexia (CAC) reduces patient survival and quality of life. Developments of efficient therapeutic strategies are required for the CAC treatments. This long-term process could be shortened by the drug-repositioning approach which exploits old drugs approved for non-cachexia disease. Amiloride, a diuretic drug, is clinically used for treatments of hypertension and edema due to heart failure. Here, we explored the effects of amiloride for ameliorating muscle wasting in murine models of cancer cachexia. Methods: CT26 and LLC tumor cells were subcutaneously injected into mice to induce cancer cachexia. Amiloride was intraperitoneally injected daily once tumors were formed. Cachexia features of the CT26 and LLC models, respectively, were characterized by phenotypic, histopathologic and biochemical analyses. Plasma exosomes and muscle atrophy-related proteins were quantitatively analyzed. Integrative NMR-based metabolomic and transcriptomic analyses were conducted to identify significantly altered metabolic pathways and distinctly changed metabolism-related biological processes in gastrocnemius. Results: The CT26 and LLC models displayed prominent cachexia features including decreases in body weight, skeletal muscle, adipose tissue and muscle strength. The amiloride treatment in tumor-bearing mice distinctly alleviated muscle atrophy and relieved cachexia-related features without affecting tumor growth. The CT26 and LLC cachexia mice showed increased particle density of plasma exosomes which were largely derived from tumors. Significantly, the amiloride treatment inhibited tumor-derived exosome release, which did not obviously affect exosome secretion from non-neoplastic tissues or induce observable systemic toxicities in normal healthy mice. Integrative-omics revealed significant metabolic impairments in cachectic gastrocnemius, including promoted muscular catabolism, inhibited muscular protein synthesis, blocked glycolysis and impeded ketone body oxidation. The amiloride treatment evidently improved the metabolic impairments in cachectic gastrocnemius. Conclusions: Our results demonstrated the efficacy of amiloride in ameliorating cachectic muscle wasting and elucidated the underlying mechanistic rationale for its use as an alternative strategy to improve CAC treatments.
2021-07-14 | GSE173250 | GEO
Project description:Cancer cachexia (CCx) is a multifactorial wasting disorder in patients with cancer characterized by involuntary body weight loss. Whereas CCx is associated with reduced quality of life and poor survival, no approved pharmacological intervention exists. Here we show that elevated circulating levels of the tumour-derived glycoprotein ADAMTSL4 were associated with weight loss in various preclinical CCx models as well as in cachectic patients with different cancers. ADAMTSL4 overexpression in non-cachexia-inducing tumour cells conferred cachexia-inducing properties upon exposure of cultured myocytes and adipocytes as well as implantation in mice. Reversely, genetic ADAMTSL4 deletion in cachexia-inducing cancer cells markedly repressed wasting phenotypes both in vitro and in vivo. Ligand-receptor capture technology identified the latency-associated peptide of TGF-β1 as ADAMTSL4 target on muscle cell surface. ADAMTSL4 mediated muscle atrophy and adipose tissue wasting through local TGF-β1 activation, sensitive to inhibition of TGFβR1 or knockdown of proTGF-β1. Given the conserved correlation between circulating ADAMTSL4 and skeletal muscle TGF pathway component expression in an independent human cancer patient cohort, our data suggest that blockade of ADAMTSL4 function represents a first rational approach towards efficient cancer cachexia pharmacotherapy.
2026-06-16 | GSE304945 | GEO
Project description:Cancer mediated activation of the ActRIIB-ALK4/5 heterodimer by myostatin is strongly associated with muscle wasting. Progressive skeletal muscle wasting, with or without loss of adipose tissue, is observed in up to 50 per cent of all cancer patients. This multifactorial syndrome is known as cachexia, and cannot be fully reversed by conventional nutritional support. Cachexia leads to progressive functional impairment. We investigated in vitro and in vivo the efficacy of ALK4/5 receptor blockers like SB431542 in preventing muscle wasting and in this context determined muscle-related miRNA expression profiles in non-tumor bearing control mice, in SB431542 treated C26 tumor-bearing mice and in cachectic C26 tumor-bearing mice.
2018-09-28 | GSE120593 | GEO
Project description:Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia associates with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models that fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA, that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology to cachectic patients. We envision the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.
2019-08-06 | GSE133524 | GEO
Project description:Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia associates with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models that fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA, that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology to cachectic patients. We envision the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.
2019-08-06 | GSE133523 | GEO
Project description:Cancer cachexia is a multifactorial condition characterized by skeletal muscle loss that impairs longevity and quality of life of the vast majority of cancer patients. However, the ability to develop therapeutic strategies to counter cachexia is impeded by the limited understanding of the underlying mechanisms of cachexia in human cancer patients. The purpose of this study was therefore to characterize the proteomic signature of skeletal muscle obtained from cachectic pancreatic ductal adenocarcinoma (PDAC) patients, who exhibit one of the highest rates of cachexia. Muscle biopsies (rectus abdominis) were obtained from PDAC patients (n=8; 70±10yr; BMI: 26.8±5.9kg･m-2) undergoing tumor resection surgery as well as age and sex-matched non-cancer controls (n=6; 66±9yr; BMI: 30.8±5.2kg･m-2). PDAC patients were cachectic (6 month body weight loss > 5%; mean: 15.7±7.9%) and did not undergo neoadjuvant therapy.
2025-06-23 | PXD047838 | Pride
Project description:Cancer cachexia is a deadly wasting syndrome that accompanies various diseases, including approximately 50% of cancers. To assess the pathological transformations that occur in the local wasting tissue microenvironment during lung cancer cachexia, we assessed changes in wasting tissues at the transcriptomic level. KEGG analysis of the up-regulated DEGs enrichment for pathways including fatty acid degradation, inflammation, and ferroptosis.
2022-01-18 | GSE188479 | GEO