{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>GSDMC Function Summary</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Gasdermin C (GSDMC) is a multifunctional member of the gasdermin family that plays diverse roles in cell death, inflammation, and cancer. In several cancer models, GSDMC can be proteolytically activated—most notably by caspase‑8—in response to signals such as tumor necrosis factor‐α stimulation or metabolic stress (e.g., by α‑ketoglutarate), thereby liberating its N‑terminal domain that forms membrane pores and induces pyroptosis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, genomic studies have revealed that low‐copy gains involving the chromosomal region harboring GSDMC—as well as adjacent elements like PVT1 and CCDC26—can contribute to oncogenesis, while in colorectal cancers GSDMC upregulation promotes tumor cell proliferation (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in lung adenocarcinoma and kidney renal clear cell carcinoma, elevated GSDMC expression has been associated with radio‐resistance, increased cellular proliferation, and poor patient survival (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and similar copy number and expression alterations have been detected in ovarian cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, studies in the gastrointestinal epithelium indicate that GSDMC is normally expressed in both differentiating and differentiated cells, where it may function in epithelial homeostasis and even act, under certain conditions, as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Outside of cancer, environmental factors such as ultraviolet irradiation can upregulate GSDMC expression in skin keratinocytes through a TRPV1‐calcium/calcineurin/NFATc1 signaling pathway; this induction is linked to increased activation of ERK and JNK and subsequent matrix metalloproteinase‑1 expression, thereby contributing to tissue remodeling in the skin"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Furthermore, genetic studies have identified variants near the GSDMC locus that correlate with musculoskeletal conditions—for instance, increased plasma and mRNA levels of GSDMC have been associated with lumbar spinal stenosis, while certain polymorphisms appear protective against lumbar disc herniation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, the evidence indicates that GSDMC serves as an important mediator of pyroptosis by engaging its pore‑forming activity, with context‐dependent roles that can promote malignant proliferation and therapy resistance in some cancers, yet also contribute to regulated cell death and tissue remodeling in non‑malignant settings. Its diverse functions highlight GSDMC as a potential prognostic biomarker and therapeutic target in inflammatory disorders and cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junwei Hou, Rongce Zhao, Weiya Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-020-0575-z"}], "href": "https://doi.org/10.1038/s41556-020-0575-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32929201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32929201"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jia-Yuan Zhang, Bo Zhou, Ru-Yue Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The metabolite α-KG induces GSDMC-dependent pyroptosis through death receptor 6-activated caspase-8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41422-021-00506-9"}], "href": "https://doi.org/10.1038/s41422-021-00506-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34012073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34012073"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuen-Yi Tseng, Branden S Moriarity, Wuming Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PVT1 dependence in cancer with MYC copy-number increase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13311"}], "href": "https://doi.org/10.1038/nature13311"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25043044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25043044"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Masashi Miguchi, Takao Hinoi, Manabu Shimomura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gasdermin C Is Upregulated by Inactivation of Transforming Growth Factor β Receptor Type II in the Presence of Mutated Apc, Promoting Colorectal Cancer Proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0166422"}], "href": "https://doi.org/10.1371/journal.pone.0166422"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27835699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27835699"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jie Wei, Zhijie Xu, Xi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of GSDMC is a prognostic factor for predicting a poor outcome in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2019.10837"}], "href": "https://doi.org/10.3892/mmr.2019.10837"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31939622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31939622"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yun-Qian Cui, Fei Meng, Wen-Li Zhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High Expression of GSDMC Is Associated with Poor Survival in Kidney Clear Cell Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/5282894"}], "href": "https://doi.org/10.1155/2021/5282894"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34778452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34778452"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jiayue Luo, Jianguo Lai "}, {"type": "b", "children": [{"type": "t", "text": "Pyroptosis-related molecular classification and immune microenvironment infiltration in breast cancer: A novel therapeutic target."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.17247"}], "href": "https://doi.org/10.1111/jcmm.17247"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35233921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35233921"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Norihisa Saeki, Takebumi Usui, Kazuhiko Aoyagi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinctive expression and function of four GSDM family genes (GSDMA-D) in normal and malignant upper gastrointestinal epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Chromosomes Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/gcc.20636"}], "href": "https://doi.org/10.1002/gcc.20636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19051310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19051310"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Novi Kusumaningrum, Dong Hun Lee, Hyun-Sun Yoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ultraviolet light-induced gasdermin C expression is mediated via TRPV1/calcium/calcineurin/NFATc1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2018.3839"}], "href": "https://doi.org/10.3892/ijmm.2018.3839"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30226565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30226565"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Novi Kusumaningrum, Dong Hun Lee, Hyun-Sun Yoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gasdermin C is induced by ultraviolet light and contributes to MMP-1 expression via activation of ERK and JNK pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdermsci.2018.01.015"}], "href": "https://doi.org/10.1016/j.jdermsci.2018.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29428815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29428815"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hua Jiang, Abu Moro, Yang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-78249-7"}], "href": "https://doi.org/10.1038/s41598-020-78249-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33273635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33273635"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jiamin Wu, Yao Sun, Zichao Xiong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of GSDMC polymorphisms with lumbar disc herniation among Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Immunogenet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/iji.12488"}], "href": "https://doi.org/10.1111/iji.12488"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32333499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32333499"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Sudipta Das, Marina Miller, David H Broide "}, {"type": "b", "children": [{"type": "t", "text": "Chromosome 17q21 Genes ORMDL3 and GSDMB in Asthma and Immune Diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/bs.ai.2017.06.001"}], "href": "https://doi.org/10.1016/bs.ai.2017.06.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28826527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28826527"}]}]}]}