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      Autophagy Modulation by Viral Infections Influences Tumor Development

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          Abstract

          Autophagy is a self-degradative process important for balancing cellular homeostasis at critical times in development and/or in response to nutrient stress. This is particularly relevant in tumor model in which autophagy has been demonstrated to have an important impact on tumor behavior. In one hand, autophagy limits tumor transformation of precancerous cells in early stage, and in the other hand, it favors the survival, proliferation, metastasis, and resistance to antitumor therapies in more advanced tumors. This catabolic machinery can be induced by an important variety of extra- and intracellular stimuli. For instance, viral infection has often been associated to autophagic modulation, and the role of autophagy in virus replication differs according to the virus studied. In the context of tumor development, virus-modulated autophagy can have an important impact on tumor cells’ fate. Extensive analyses have shed light on the molecular and/or functional complex mechanisms by which virus-modulated autophagy influences precancerous or tumor cell development. This review includes an overview of discoveries describing the repercussions of an autophagy perturbation during viral infections on tumor behavior.

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          A role for mitochondria in NLRP3 inflammasome activation.

          An inflammatory response initiated by the NLRP3 inflammasome is triggered by a variety of situations of host 'danger', including infection and metabolic dysregulation. Previous studies suggested that NLRP3 inflammasome activity is negatively regulated by autophagy and positively regulated by reactive oxygen species (ROS) derived from an uncharacterized organelle. Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome. Resting NLRP3 localizes to endoplasmic reticulum structures, whereas on inflammasome activation both NLRP3 and its adaptor ASC redistribute to the perinuclear space where they co-localize with endoplasmic reticulum and mitochondria organelle clusters. Notably, both ROS generation and inflammasome activation are suppressed when mitochondrial activity is dysregulated by inhibition of the voltage-dependent anion channel. This indicates that NLRP3 inflammasome senses mitochondrial dysfunction and may explain the frequent association of mitochondrial damage with inflammatory diseases.
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            Biological Functions of Autophagy Genes: A Disease Perspective

            The lysosomal degradation pathway of autophagy plays a fundamental role in cellular, tissue, and organismal homeostasis and is mediated by evolutionarily conserved autophagy-related (ATG) genes. Definitive etiological links exist between mutations in genes that control autophagy and human disease, especially neurodegenerative, inflammatory disorders and cancer. Autophagy selectively targets dysfunctional organelles, intracellular microbes, and pathogenic proteins, and deficiencies in these processes may lead to disease. Moreover, ATG genes have diverse physiologically important roles in other membrane-trafficking and signaling pathways. This Review discusses the biological functions of autophagy genes from the perspective of understanding-and potentially reversing-the pathophysiology of human disease and aging.
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              HIF-1α pathway: role, regulation and intervention for cancer therapy

              Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O2 levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1412273
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                22 October 2021
                2021
                : 11
                : 743780
                Affiliations
                [1] 1 Institut National de la Santé et de la Recherche Médicale (INSERM), UMRS1138, Centre de Recherche des Cordeliers , Paris, France
                [2] 2 Sorbonne Université, Univ Paris , Paris, France
                [3] 3 Department of Thoracic Surgery, Hospital Cochin Assistance Publique Hopitaux de Paris , Paris, France
                Author notes

                Edited by: Chris Albanese, Georgetown University, United States

                Reviewed by: Manuela Antonioli, Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IRCCS), Italy; Susana Romero-Garcia, Universidad Nacional Autónoma de México, Mexico

                *Correspondence: Pierre-Emmanuel Joubert, pierre-emmanuel.joubert@ 123456sorbonne-universite.fr

                This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2021.743780
                8569469
                ef5106fb-b93e-4b84-b258-a513ea2d9445
                Copyright © 2021 Leonardi, Sibéril, Alifano, Cremer and Joubert

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 July 2021
                : 27 September 2021
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 247, Pages: 19, Words: 9146
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                tumor development and progression,autophagy,viral infection,oncolytic virus,oncogenic virus,immunity,tumor resistance,tumorigenesis

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