ArticleCell death & disease2021
Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 54 citations in OpenAlex.
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- SARIFA and Lipid Metabolic Reprogramming in Prostate Cancer: Fundamental Mechanisms, Tumor Microenvironment, and Novel Biomarker Prospects.Life (Basel, Switzerland) · 2026Review
- Otopetrin 1 protects against adipose tissue wasting during cancer cachexia progression.iScience · 2026Article
- Burn-associated metabolic dysfunction: could extracellular vesicles play a role?Clinical science (London, England : 1979) · 2026Review
- 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
- CircAMOTL1 promotes adipose lipolysis and browning in cancer cachexia through miR-211-5p-mediated TET2 activation.The Journal of biological chemistry · 2026Article
- White-to-brown adipose switching promotes bladder cancer progression.Neoplasia (New York, N.Y.) · 2026Article
- Extracellular vesicles in cancer-associated cachexia: molecular mechanisms and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- EV-Mediated Oncogenic Regulation in Lung Cancer and Clinical Translation: From Liquid Biopsy to Targeted Delivery Systems.International journal of nanomedicine · 2026Review
- Regulation of metabolic adaptation and leukemia progression by MUSASHI2-DEPTOR-KIF11 axis.Leukemia · 2025Article
- Article
- Lipid metabolism and lipid signaling in extracellular vesicles ontogeny: from biogenesis to functional execution.Journal of nanobiotechnology · 2025Review
- Physical Activity, Exerkines, and Their Role in Cancer Cachexia.International journal of molecular sciences · 2025Review
- Extracellular vesicles from ovarian cancer cells induce senescent lipid-laden macrophages to facilitate omental metastasis.Journal of nanobiotechnology · 2025Article
- The role of natural compounds in modulation of small extracellular vesicle biogenesis and lipid metabolism in cancer.Frontiers in molecular biosciences · 2025Review
- HO-1-Enriched Lung-Derived Exosomes Mediate Cognitive Impairment in a Mice Model of COPD Exacerbation.Canadian respiratory journal · 2025Article
- PTHrP Promotes RBP4 Expression Under the Control of PPARγ in the Kidney.International journal of molecular sciences · 2024Article
- GRP75 triggers white adipose tissue browning to promote cancer-associated cachexia.Signal transduction and targeted therapy · 2024Article
- Recent advances to address challenges in extracellular vesicle-based applications for lung cancer.Acta pharmaceutica Sinica. B · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.
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