Dataset Information

Label-free proteomic analysis of apoptotic, necrotic and necroptotic DAMPs from HNSCC cells

ABSTRACT: Necroptosis is a newly discovered form of programmed cell death (PCD) showing necrotic features, including membrane permeabilization and the release of damage-associated molecular patterns (DAMPs). Studies have revealed both its tumorigenic role and therapeutic potential in various cancers, yet its impact on head and neck squamous cell carcinoma (HNSCC) is poorly understood. To investigate the differential composition of necroptotic DAMPs, SCC25 cells treated by TNF-α+Smac mimetic (TS), TNF-α+Smac mimetic+zVAD-fmk (TSZ) and Freeze-Thaw (FT) to induce apoptosis, necroptosis and necrosis respectively. Mass spectrum analysis was used to compare the differential compositions among DAMPs derived from apoptosis (TS), necroptosis (TSZ) and necrosis (FT).

ORGANISM(S): Homo Sapiens

SUBMITTER: Yujie Liang

PROVIDER: PXD035379 | iProX | Sat Jul 16 00:00:00 BST 2022

REPOSITORIES: iProX

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Publications

cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer.

Li Jingyuan J Tan Jun J Wang Tao T Yu Shan S Guo Guangliang G Li Kan K Yang Le L Zeng Bin B Mei Xueying X Gao Siyong S Lao Xiaomei X Zhang Sien S Liao Guiqing G Liang Yujie Y

Experimental hematology & oncology 20240626 1

<h4>Background</h4>Cancer cells frequently evolve necroptotic resistance to overcome various survival stress during tumorigenesis. However, we have previously showed that necroptosis is widespread in head and neck squamous cell carcinoma (HNSCC) and contributes to tumor progression and poor survival via DAMPs-induced migration and invasiveness in peri-necroptotic tumor cells. This implicated an alternative strategy that cancers cope with necroptotic stress by reprogramming a pro-invasive necropt ...[more]

PMID: 38926796

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Project description:COVID-19 has rapidly circulated around the globe and caused significant morbidity and mortality. The disease is characterized by excessive production of pro-inflammatory cytokines and acute lung damage and patient mortality. Although initial cytokine cascades may be beneficial to the host for clearing the virus, enhanced production of pro-inflammatory cytokines and increasing levels in the systemic circulation, referred to as cytokine storm, can promote tissue damage by inducing inflammatory cell death in both infected and bystander cells. Of the multiple inflammatory cytokines produced by innate immune cells during SARS-CoV-2 infection, we found that the combination of TNF-α and IFN-γ specifically induced cell death characterized by GSDME¬–mediated pyroptosis, caspase-8–mediated apoptosis, and MLKL–mediated necroptosis. Cells deficient in both RIPK3 and caspase-8 or RIPK3 and FADD were resistant to this cell death. However, deletion of pyroptosis, apoptosis, or necroptosis individually was not sufficient to protect against cell death. Mechanistically, the STAT1/IRF1 axis activated by TNF-α and IFN-γ co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of inflammatory cell death protected mice from TNF-α and IFN-γ–induced lethal cytokine shock that mirrors the pathological symptoms of COVID-19. To determine the physiological relevance of protection, we neutralized both TNF-α and IFN-γ in multiple disease models associated with cytokine storm and found that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models. Collectively, our findings reveal that blocking the COVID-19 cytokine-mediated inflammatory cell death signaling pathway identified in this study may benefit patients with COVID-19 or other cytokine storm-driven syndromes by limiting inflammation and tissue damage. Additionally, these results open new avenues for the treatment of other infectious and autoinflammatory diseases and cancer where TNF-α and IFN-γ synergism play key pathological roles.

Dataset Information

Label-free proteomic analysis of apoptotic, necrotic and necroptotic DAMPs from HNSCC cells

Publications

cGAS-ISG15-RAGE axis reprogram necroptotic microenvironment and promote lymphatic metastasis in head and neck cancer.

Similar Datasets

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