PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.
PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment.
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DOI：
10.1038/s41418-022-01095-9
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发表时间：
2023-03
影响因子：
12.4
通讯作者：
Giorgi, Carlotta
中科院分区：
文献类型：
--
作者：
Missiroli, Sonia;Perrone, Mariasole;Gafa, Roberta;Nicoli, Francesco;Bonora, Massimo;Morciano, Giampaolo;Boncompagni, Caterina;Marchi, Saverio;Lebiedzinska-Arciszewska, Magdalena;Vezzani, Bianca;Lanza, Giovanni;Kricek, Franz;Borghi, Alessandro;Fiorica, Francesco;Ito, Keisuke;Wieckowski, Mariusz R.;Di Virgilio, Francesco;Abelli, Luigi;Pinton, Paolo;Giorgi, Carlotta
肿瘤微环境（TME）引起的不受控制的炎症反应显著促进癌症进展，促使对反调节机制进行调查和仔细评估。我们确定了一个三聚体的复合物在乳腺癌相关膜（MAMs），其中嘌呤能P2 X7受体-NLRP 3炎性小体联络是微调的肿瘤抑制PML。PML下调由于P2 X7 R-NLRP 3抑制的丧失而导致免疫反应加剧，从而促进肿瘤生长。来自MAMs的PML错误定位导致不受控制的NLRP 3活化，以及随后的细胞因子爆炸助长癌症并使不同人类癌症中的肿瘤预后恶化。为PML-P2 X7 R-NLRP 3轴提供了新的机制见解，以控制人类致癌过程中的TME，从而促进新的靶向治疗方法。
Uncontrolled inflammatory response arising from the tumor microenvironment (TME) significantly contributes to cancer progression, prompting an investigation and careful evaluation of counter-regulatory mechanisms. We identified a trimeric complex at the mitochondria-associated membranes (MAMs), in which the purinergic P2X7 receptor - NLRP3 inflammasome liaison is fine-tuned by the tumor suppressor PML. PML downregulation drives an exacerbated immune response due to a loss of P2X7R-NLRP3 restraint that boosts tumor growth. PML mislocalization from MAMs elicits an uncontrolled NLRP3 activation, and consequent cytokines blast fueling cancer and worsening the tumor prognosis in different human cancers. New mechanistic insights are provided for the PML-P2X7R-NLRP3 axis to govern the TME in human carcinogenesis, fostering new targeted therapeutic approaches.
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影响因子：
64.8
作者：
Kuchay S;Giorgi C;Simoneschi D;Pagan J;Missiroli S;Saraf A;Florens L;Washburn MP;Collazo-Lorduy A;Castillo-Martin M;Cordon-Cardo C;Sebti SM;Pinton P;Pagano M
通讯作者：
Pagano M
影响因子：
5.4
作者：
Scherer, Myriam;Stamminger, Thomas
通讯作者：
Stamminger, Thomas
影响因子：
5.2
作者：
Missiroli S;Perrone M;Boncompagni C;Borghi C;Campagnaro A;Marchetti F;Anania G;Greco P;Fiorica F;Pinton P;Giorgi C
通讯作者：
Giorgi C
DOI：
10.1126/science.1189157
发表时间：
2010-11-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Giorgi C;Ito K;Lin HK;Santangelo C;Wieckowski MR;Lebiedzinska M;Bononi A;Bonora M;Duszynski J;Bernardi R;Rizzuto R;Tacchetti C;Pinton P;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
9
作者：
Missiroli S;Patergnani S;Caroccia N;Pedriali G;Perrone M;Previati M;Wieckowski MR;Giorgi C
通讯作者：
Giorgi C