Dataset Information

Myeloid PTEN promotes chemotherapy-induced NLRP3 inflammasome activation and antitumor immunity

ABSTRACT: In this study, we found that myeloid PTEN can determine chemotherapy responsiveness by promoting NLRP3-dependent antitumor immunity and suggest that it might be a potential biomarker to predict the chemotherapy responses and manipulating NLRP3/IL-1might be able to overcome the chemotherapy resistance in PTEN-loss patients.

ORGANISM(S): Homo Sapiens

SUBMITTER: Rongbin Zhou

PROVIDER: PXD018597 | iProX | Thu Apr 16 00:00:00 BST 2020

REPOSITORIES: iProX

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Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity.

Huang Yi Y Wang Huanyu H Hao Yize Y Lin Hualong H Dong Menghao M Ye Jin J Song Lei L Wang Yunzhi Y Li Qingqing Q Shan Benjie B Jiang Yizhou Y Li Hongqi H Shao Zhiming Z Kroemer Guido G Zhang Huafeng H Bai Li L Jin Tengchuan T Wang Chao C Ma Yuting Y Cai Yongping Y Ding Chen C Liu Suling S Pan Yueyin Y Jiang Wei W Zhou Rongbin R

Nature cell biology 20200504 6

PTEN is a dual-specificity phosphatase that is frequently mutated in human cancer, and its deficiency in cancer has been associated with therapy resistance and poor survival. Although the intrinsic tumour-suppressor function of PTEN has been well established, evidence of its role in the tumour immune microenvironment is lacking. Here, we show that chemotherapy-induced antitumour immune responses and tumour suppression rely on myeloid-cell PTEN, which is essential for chemotherapy-induced activat ...[more]

PMID: 32367047

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Project description:Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1beta (IL1B) maturation. The activation of NLRP3 inflammasome requires two-step signals. The first “priming” signal (Signal 1) enhances gene expression of inflammasome components. The second “activation” signal (Signal 2) promotes the assembly of inflammasome components. Deregulated activation of NLRP3 inflammasome contributes to the pathological processes of Alzheimer’s disease (AD) and multiple sclerosis (MS). However, at present, the precise mechanism regulating NLRP3 inflammasome activation and deactivation remains largely unknown. By genome-wide gene expression profiling, we studied the molecular network of NLRP3 inflammasome activation-responsive genes in a human monocyte cell line THP-1 sequentially given two-step signals. We identified the set of 83 NLRP3 inflammasome activation-responsive genes. Among them, we found the NR4A nuclear receptor family NR4A1, NR4A2, and NR4A3, the EGR family EGR1, EGR2, and EGR3, the IkappaB family NFKBIZ, NFKBID, and NFKBIA as a key group of the genes that possibly constitute a negative feedback loop for shutting down inflammation following NLRP3 inflammasome activation. By molecular network analysis, we identified a complex network of NLRP3 inflammasome activation-responsive genes involved in cellular development and death, and immune and inflammatory responses, where transcription factors AP-1, NR4A, and EGR serve as a hub. Thus, NLRP3 inflammasome activation-responsive genes constitute the molecular network composed of a set of negative feedback regulators for prompt resolution of inflammation. To load the Signal 1 (S1), THP-1 cells were incubated for 3 hours in the culture medium with or without inclusion of 0.2 microgram/ml lipopolysaccharide (LPS). To load the Signal 2 (S2), they were incubated further for 2 hours in the culture medium with inclusion of 10 microM nigericin sodium salt dissolved in ethanol or the equal v/v% concentration of ethanol (vehicle), followed by processing for microarray analysis on Human Gene 1.0 ST Array (Affymetrix).

Dataset Information

Myeloid PTEN promotes chemotherapy-induced NLRP3 inflammasome activation and antitumor immunity

Publications

Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity.

Similar Datasets

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