GEO series
Tumor-borne ADAMTSL4 drives cancer cachexia via TGFβ signaling pathway
GSE304945
Mus musculus
Expression profiling by high throughput sequencing
32 samples
Submitted 2026/06/16
Platform GPL24247
Summary
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.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE304945_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 32 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1303573 and SRA study SRP607586. Searching any of these in the dataset finder brings you back here.
Study design
32 conditions, each sampled once — no replicated groups
Read from 32 sample titles: 32 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9160024 MC38AG_1_GC Muscle
- GSM9160025 MC38AG_2_GC Muscle
- GSM9160026 MC38AG_3_GC Muscle
- GSM9160027 MC38AG_4_GC Muscle
- GSM9160028 MC38AG_5_GC Muscle
- GSM9160029 MC38CG_1_GC Muscle
- GSM9160030 MC38CG_2_GC Muscle
- GSM9160031 MC38CG_3_GC Muscle
- GSM9160032 MC38CG_4_GC Muscle
- GSM9160033 MC38CG_5_GC Muscle
- GSM9160034 C26shAG_1_GC Muscle
- GSM9160035 C26shAG_2_GC Muscle
- GSM9160036 C26shAG_3_GC Muscle
- GSM9160037 C26shAG_4_GC Muscle
- GSM9160038 C26shAG_5_GC Muscle
- GSM9160039 C26shCG_1_GC Muscle
- GSM9160040 C26shCG_2_GC Muscle
- GSM9160041 C26shCG_3_GC Muscle
- GSM9160042 C26shCG_4_GC Muscle
- GSM9160043 C26shCG_5_GC Muscle
- GSM9160044 PBSG_1_GC Muscle
- GSM9160045 PBSG_2_GC Muscle
- GSM9160046 C26shAA_1_eWAT
- GSM9160047 C26shAA_2_eWAT
- GSM9160048 C26shAA_3_eWAT
- GSM9160049 C26shCA_1_eWAT
- GSM9160050 C26shCA_2_eWAT
- GSM9160051 C26shCA_3_eWAT
- GSM9809105 C26shAS_1_iWAT
- GSM9809106 C26shAS_2_iWAT
- GSM9809107 C26shCS_1_iWAT
- GSM9809108 C26shCS_2_iWAT
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