ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Caspase-6/Gasdermin C-Mediated Tumor Cell Pyroptosis Promotes Colorectal Cancer Progression Through CXCL2-Dependent Recruitment of Myeloid-Derived Suppressor Cells.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Theme and variations: activation and regulation of gasdermin-mediated inflammation.Biochemical Society transactions · 2026Review
- STAT3 interference-driven nanomodulators reverse lipid metabolism-associated chemoresistance and potentiate metalloimmunotherapy in breast cancer.Cell reports. Medicine · 2026Article
- A pyroptosis-related molecular signature stratifies prognosis and highlights GSDMB-mediated malignancy in intrahepatic cholangiocarcinoma.Biology direct · 2026Article
- The Paradoxical Role of Pyroptosis in Gastrointestinal Cancers: From Molecular Mechanisms to Therapeutic Horizons.Biomedicines · 2026Review
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Review
- Involvement of the pyroptosis-HMGB1 axis in systemic diseases.Frontiers in cell and developmental biology · 2026Review
- Optimized detection of caspase-6 activation in a murine inflammation model to inform neurodegenerative disease therapies.PloS one · 2026Article
- The tumor immune microenvironment of thyroid cancer and colorectal cancer: cellular crosstalk and therapeutic implications.Frontiers in immunology · 2026Review
- Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Caspases and programmed cell death in sepsis: mechanisms, pathophysiology, and therapeutic targets.Frontiers in immunology · 2026Review
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- Regulated cell death in cancer: Mechanisms, crosstalk, and opportunities for therapy.Cancer letters · 2025Review
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity.Immunity · 2025Article
- Caspase-6/Gasdermin C-Mediated Tumor Cell Pyroptosis Promotes Colorectal Cancer Progression Through CXCL2-Dependent Recruitment of Myeloid-Derived Suppressor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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12 authors.
Funding
Abstract
Gasdermin (GSDM) family proteins mediate inflammatory cell pyroptosis and exert critical contributions to the pathogenesis of gastrointestinal cancers, infections, and gut mucosal inflammation. Gasdermin C (GSDMC) is overexpressed in human colorectal cancer (CRC); however, the molecular mechanisms underlying GSDMC regulation of CRC tumorigenesis are largely elusive. Here, it is found that both GSDMC expression and activation are significantly elevated in human and mouse CRC tissues. Gsdmc2/3/4 deficiency attenuates tumor progression in both chemically induced CRC mouse model and spontaneous intestinal tumor model. Mechanistically, under hypoxia and low-glucose condition, GSDMC2/3/4 are directly activated by Caspase-6, but not by Caspase-8, as previously reported in other cancers. GSDMC2/3/4-mediated pyroptosis in tumor cells leads to the release of high mobility group protein B1 (HMGB1), which enhances the expression of chemokine attractant C-X-C motif chemokine 2 (CXCL2) in surrounding tumor cells. Subsequently, the elevated CXCL2 secretion from tumor cells promotes the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment (TME) through C-X-C chemokine receptor type 2 (CXCR2), thereby facilitating CRC progression. These findings reveal a mechanism by which Caspase-6/GSDMC-mediated tumor cell pyroptosis, in response to hypoxic and low-glucose conditions, remodels the immunosuppressive microenvironment through CXCL2-dependent recruitment of MDSCs. These results identify GSDMC as a potential drug target for CRC therapy.
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