ArticleJCI insight2018
Calpain-6 controls the fate of sarcoma stem cells by promoting autophagy and preventing senescence.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- TGF-β Induced by Allergic Lung Inflammation Enhances Os-Teosarcoma Lung Metastasis in a Mouse Comorbidity Model.International journal of molecular sciences · 2025Article
- Targeting KIFC1 Promotes Senescence in Soft Tissue Sarcoma via FXR1-Dependent Regulation of MAD2L1 mRNA Stability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Calpain and Cardiometabolic Diseases.International journal of molecular sciences · 2023Review
- Autophagy Modulation as a Potential Therapeutic Strategy in Osteosarcoma: Current Insights and Future Perspectives.International journal of molecular sciences · 2023Review
- H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt/β-catenin and TGF-β pathways.Reproductive biology and endocrinology : RB&E · 2023Review
- Novel insights into the progression and prognosis of the calpain family members in hepatocellular carcinoma: a comprehensive integrated analysis.Frontiers in molecular biosciences · 2023Article
- A calpain-6/YAP axis in sarcoma stem cells that drives the outgrowth of tumors and metastases.Cell death & disease · 2022Article
- Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers.Cancers · 2022Review
- Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model.International journal of molecular medicine · 2021Article
- CAPN6 in disease: An emerging therapeutic target (Review).International journal of molecular medicine · 2020Review
- Article
- Non-proteolytic calpain-6 interacts with VEGFA and promotes angiogenesis by increasing VEGF secretion.Scientific reports · 2019Article
- Deficiency of calpain-6 inhibits primary ciliogenesis.BMB reports · 2019Article
- Role of autophagy in osteosarcoma.Journal of bone oncology · 2019Review
- CAGE-miR-140-5p-Wnt1 Axis Regulates Autophagic Flux, Tumorigenic Potential of Mouse Colon Cancer Cells and Cellular Interactions Mediated by Exosomes.Frontiers in oncology · 2019Article
- Killing Two Angry Birds with One Stone: Autophagy Activation by Inhibiting Calpains in Neurodegenerative Diseases and Beyond.BioMed research international · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sarcomas are still unsolved therapeutic challenges. Cancer stem cells are believed to contribute to sarcoma development, but lack of specific markers prevents their characterization and targeting. Here, we show that calpain-6 expression is associated with cancer stem cell features. In mouse models of bone sarcoma, calpain-6-expressing cells have unique tumor-initiating and metastatic capacities. Calpain-6 levels are especially high in tumors that have been successfully propagated in mouse to establish patient-derived xenografts. We found that calpain-6 levels are increased by hypoxia in vitro and calpain-6 is detected within hypoxic areas in tumors. Furthermore, calpain-6 expression depends on the stem cell transcription network that involves Oct4, Nanog, and Sox2 and is activated by hypoxia. Calpain-6 knockdown blocks tumor development in mouse and induces depletion of the cancer stem cell population. Data from transcriptomic analyses reveal that calpain-6 expression in sarcomas inversely correlates with senescence markers. Calpain-6 knockdown suppresses hypoxia-dependent prevention of senescence entry and also promotion of autophagic flux. Together, our results demonstrate that calpain-6 identifies sarcoma cells with stem-like properties and is a mediator of hypoxia to prevent senescence, promote autophagy, and maintain the tumor-initiating cell population. These findings open what we believe is a novel therapeutic avenue for targeting sarcoma stem cells.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.