ArticleSignal transduction and targeted therapy2024
GRP75 triggers white adipose tissue browning to promote cancer-associated cachexia.
Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- [Recent Advances in the Interorgan Regulatory Roles of Adipose Tissue].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Pooled it
- Targeting LDHA Palmitoylation Sensitizes GBM to Chemoradiotherapy via Suppressing Palmitic Acid Induced Glycolytic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting GRP75 by natural compound polyphyllin II triggers mitochondrial calcium overload and pyroptosis to potentiate cancer immunotherapy.Journal for immunotherapy of cancer · 2026Article
- The pro-tumorigenic functions of cancer-associated adipocytes are dependent on the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1.Signal transduction and targeted therapy · 2026Article
- Otopetrin 1 protects against adipose tissue wasting during cancer cachexia progression.iScience · 2026Article
- Article
- Cancer cachexia induces senescent reprogramming of brown adipose tissue and pro-cachectic S100A9 secretion by adipocytes.Cell death & disease · 2026Article
- C26 and CT26 colorectal cancer models exhibit divergent cachexia phenotypes, intramuscular inflammation, and protein turnover signaling.bioRxiv : the preprint server for biology · 2026Article
- Nanomedicine novel strategies: deciphering the EV-metabolic axis as a natural nanocarrier network in lung cancer progression and cachexia.Journal of nanobiotechnology · 2026Review
- Fueling or Fighting Cancer? The Thermogenic Paradox of Brown Adipose Tissue.Current obesity reports · 2026Review
- Separating anorexia -dependent and -independent effects in cancer cachexia.bioRxiv : the preprint server for biology · 2026Article
- CircAMOTL1 promotes adipose lipolysis and browning in cancer cachexia through miR-211-5p-mediated TET2 activation.The Journal of biological chemistry · 2026Article
- A2-pancortins interact with Bcl-xL and WAVE1 to promote mitochondria-ER contact sites (MERCs) and exacerbate mitochondrial calcium elevation to mediate cell death in stroke.Scientific reports · 2026Article
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment.Frontiers in immunology · 2026Review
- Extracellular vesicles in cancer-associated cachexia: molecular mechanisms and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- Adipose-Muscle Crosstalk in COPD Cachexia: Early Adipose Atrophy Drives Subsequent Muscle Wasting.Journal of cachexia, sarcopenia and muscle · 2025Article
- Cancer-Associated Cachexia in the Era of Obesity.International journal of molecular sciences · 2025Review
- GRP-based vaccines as a novel approach in cancer immunotherapy: mechanisms, challenges, and prospects.Cancer cell international · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Cachexia, which affects 50-80% of cancer patients, is a debilitating syndrome that leads to 20% of cancer-related deaths. A key feature of cachexia is adipose tissue atrophy, but how it contributes to the development of cachexia is poorly understood. Here, we demonstrate in mouse models of cancer cachexia that white adipose tissue browning, which can be a characteristic early-onset manifestation, occurs prior to the loss of body weight and skeletal muscle wasting. By analysing the proteins differentially expressed in extracellular vesicles derived from cachexia-inducing tumours, we identified a molecular chaperone, Glucose-regulated protein 75 (GRP75), as a critical mediator of adipocyte browning. Mechanistically, GRP75 binds adenine nucleotide translocase 2 (ANT2) to form a GRP75-ANT2 complex. Strikingly, stabilized ANT2 enhances its interaction with uncoupling protein 1, leading to elevated expression of the latter, which, in turn, promotes adipocyte browning. Treatment with withanone, a GRP75 inhibitor, can reverse this browning and alleviate cachectic phenotypes in vivo. Overall, our findings reveal a novel mechanism by which tumour-derived GRP75 regulates white adipose tissue browning during cachexia development and suggest a potential white adipose tissue-centred targeting approach for early cachexia intervention.
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