Proteomics

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ITRAQ-based MS analysis of nasopharyngeal carcinoma cells with inflammasome activation


ABSTRACT: We previously reported that tumor-cell inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable ASC specks and govern the cellular secretion of IL-1. However, we know little about the biological and biochemical differences between cells with and without ASC speck formation. In this study, we used proteomic iTRAQ analysis to analyze the proteomes of NPC cells that differ in their apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation upon cisplatin treatment. We identified proteins that were differentially over-expressed in cells with specks, and found that they fell into two Gene ontology (GO) pathways: mitochondrial oxidative phosphorylation (OxPhos) and ubiquinone metabolism. We observed up-regulation of various components of the OxPhos machinery (including NDUFB3, NDUFB8 and ATP5B), and subsequently found that these changes lead to mitochondrial ROS (mtROS) production, which promotes the formation and activation of NLRP3 inflammasomes and subsequent pyroptosis. In NPC patients with [Define this term?] high-NLRP3 tumors, better recurrence-free survival was significantly associated with high-level expression of NDUFB8 (P=0.037) and ATP5B (P=0.029), as examined using immunohistochemistry. Together, our results demonstrate that upregulated mitochondrial OxPhos components are strongly associated with NLRP3 inflammasome activation in NPC. Our findings further suggest that high-level expression of OxPhos components could be prognostic markers and/or promising therapeutic targets in patients with NPC.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Chih-Ching Wu  

LAB HEAD: Chih-Ching Wu

PROVIDER: PXD013071 | Pride | 2019-11-15

REPOSITORIES: Pride

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Publications

Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma.

Chung I-Che IC   Chen Lih-Chyang LC   Tsang Ngan-Ming NM   Chuang Wen-Yu WY   Liao Tzu-Chieh TC   Yuan Sheng-Ning SN   OuYang Chun-Nan CN   Ojcius David M DM   Wu Chih-Ching CC   Chang Yu-Sun YS  

Molecular & cellular proteomics : MCP 20191113 1


We previously reported that tumor inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable specks and govern the cellular secretion of IL-1β. However, we know little about the biological and biochemical differences between cells with and without apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation. In this study, we used proteom  ...[more]

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