PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment

Sonia Missiroli, Mariasole Perrone, Roberta Gafà, Francesco Nicoli, Massimo Bonora, Giampaolo Morciano, Caterina Boncompagni, Saverio Marchi, Magdalena Lebiedzinska-Arciszewska, Bianca Vezzani, Giovanni Lanza, Franz Kricek, Alessandro Borghi, Francesco Fiorica, Keisuke Ito, Mariusz R. Wieckowski, Francesco Di Virgilio, Luigi Abelli, Paolo Pinton, Carlotta Giorgi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalCell Death and Differentiation
DOIs
StateAccepted/In press - 2022

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'PML at mitochondria-associated membranes governs a trimeric complex with NLRP3 and P2X7R that modulates the tumor immune microenvironment'. Together they form a unique fingerprint.

Cite this