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Autophagy in malignant transformation and cancer progression

Identifieur interne : 000318 ( Istex/Corpus ); précédent : 000317; suivant : 000319

Autophagy in malignant transformation and cancer progression

Auteurs : Lorenzo Galluzzi ; Federico Pietrocola ; José Manuel Bravo-San Pedro ; Ravi K. Amaravadi ; Eric H. Baehrecke ; Francesco Cecconi ; Patrice Codogno ; Jayanta Debnath ; David A. Gewirtz ; Vassiliki Karantza ; Alec Kimmelman ; Sharad Kumar ; Beth Levine ; Maria Chiara Maiuri ; Seamus J. Martin ; Josef Penninger ; Mauro Piacentini ; David C. Rubinsztein ; Hans-Uwe Simon ; Anne Simonsen ; Andrew M. Thorburn ; Guillermo Velasco ; Kevin M. Ryan ; Guido Kroemer

Source :

RBID : ISTEX:1DD0F6A1097CF6D38BD562148AEBD9804AA41BFD

Abstract

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.
Autophagy has been described to have tumor‐suppressive as well as tumor‐promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy.

Url:
DOI: 10.15252/embj.201490784

Links to Exploration step

ISTEX:1DD0F6A1097CF6D38BD562148AEBD9804AA41BFD

Le document en format XML

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<name sortKey="Bravo An Pedro, Jose Manuel" sort="Bravo An Pedro, Jose Manuel" uniqKey="Bravo An Pedro J" first="José Manuel" last="Bravo-San Pedro">José Manuel Bravo-San Pedro</name>
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<name sortKey="Cecconi, Francesco" sort="Cecconi, Francesco" uniqKey="Cecconi F" first="Francesco" last="Cecconi">Francesco Cecconi</name>
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<name sortKey="Codogno, Patrice" sort="Codogno, Patrice" uniqKey="Codogno P" first="Patrice" last="Codogno">Patrice Codogno</name>
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<name sortKey="Debnath, Jayanta" sort="Debnath, Jayanta" uniqKey="Debnath J" first="Jayanta" last="Debnath">Jayanta Debnath</name>
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<name sortKey="Gewirtz, David A" sort="Gewirtz, David A" uniqKey="Gewirtz D" first="David A" last="Gewirtz">David A. Gewirtz</name>
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<name sortKey="Karantza, Vassiliki" sort="Karantza, Vassiliki" uniqKey="Karantza V" first="Vassiliki" last="Karantza">Vassiliki Karantza</name>
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<name sortKey="Kimmelman, Alec" sort="Kimmelman, Alec" uniqKey="Kimmelman A" first="Alec" last="Kimmelman">Alec Kimmelman</name>
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<name sortKey="Kumar, Sharad" sort="Kumar, Sharad" uniqKey="Kumar S" first="Sharad" last="Kumar">Sharad Kumar</name>
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<name sortKey="Levine, Beth" sort="Levine, Beth" uniqKey="Levine B" first="Beth" last="Levine">Beth Levine</name>
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<mods:affiliation>Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA</mods:affiliation>
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<name sortKey="Maiuri, Maria Chiara" sort="Maiuri, Maria Chiara" uniqKey="Maiuri M" first="Maria Chiara" last="Maiuri">Maria Chiara Maiuri</name>
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<name sortKey="Penninger, Josef" sort="Penninger, Josef" uniqKey="Penninger J" first="Josef" last="Penninger">Josef Penninger</name>
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<mods:affiliation>National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy</mods:affiliation>
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<name sortKey="Rubinsztein, David C" sort="Rubinsztein, David C" uniqKey="Rubinsztein D" first="David C" last="Rubinsztein">David C. Rubinsztein</name>
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<mods:affiliation>Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</mods:affiliation>
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<name sortKey="Simon, Hans We" sort="Simon, Hans We" uniqKey="Simon H" first="Hans-Uwe" last="Simon">Hans-Uwe Simon</name>
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<name sortKey="Simonsen, Anne" sort="Simonsen, Anne" uniqKey="Simonsen A" first="Anne" last="Simonsen">Anne Simonsen</name>
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<mods:affiliation>Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway</mods:affiliation>
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<name sortKey="Thorburn, Andrew M" sort="Thorburn, Andrew M" uniqKey="Thorburn A" first="Andrew M" last="Thorburn">Andrew M. Thorburn</name>
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<mods:affiliation>Department of Pharmacology, University of Colorado School of Medicine, CO, Aurora, USA</mods:affiliation>
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<name sortKey="Velasco, Guillermo" sort="Velasco, Guillermo" uniqKey="Velasco G" first="Guillermo" last="Velasco">Guillermo Velasco</name>
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<mods:affiliation>Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University of Madrid, Madrid, Spain</mods:affiliation>
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<mods:affiliation>Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain</mods:affiliation>
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<name sortKey="Ryan, Kevin M" sort="Ryan, Kevin M" uniqKey="Ryan K" first="Kevin M" last="Ryan">Kevin M. Ryan</name>
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<mods:affiliation>Cancer Research UK Beatson Institute, Glasgow, UK</mods:affiliation>
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<name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name>
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<mods:affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>INSERM, U1138, Paris, France</mods:affiliation>
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<affiliation>
<mods:affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</mods:affiliation>
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<mods:affiliation>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP‐HP, Paris, France</mods:affiliation>
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<mods:affiliation>Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France</mods:affiliation>
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<name sortKey="Pietrocola, Federico" sort="Pietrocola, Federico" uniqKey="Pietrocola F" first="Federico" last="Pietrocola">Federico Pietrocola</name>
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<mods:affiliation>Gustave Roussy Cancer Campus, Villejuif, France</mods:affiliation>
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<name sortKey="Bravo An Pedro, Jose Manuel" sort="Bravo An Pedro, Jose Manuel" uniqKey="Bravo An Pedro J" first="José Manuel" last="Bravo-San Pedro">José Manuel Bravo-San Pedro</name>
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<mods:affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</mods:affiliation>
</affiliation>
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<mods:affiliation>INSERM, U1138, Paris, France</mods:affiliation>
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<mods:affiliation>Gustave Roussy Cancer Campus, Villejuif, France</mods:affiliation>
</affiliation>
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<name sortKey="Amaravadi, Ravi K" sort="Amaravadi, Ravi K" uniqKey="Amaravadi R" first="Ravi K" last="Amaravadi">Ravi K. Amaravadi</name>
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<mods:affiliation>Abramson Cancer Center, University of Pennsylvania, PA, Philadelphia, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Baehrecke, Eric H" sort="Baehrecke, Eric H" uniqKey="Baehrecke E" first="Eric H" last="Baehrecke">Eric H. Baehrecke</name>
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<mods:affiliation>Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, MA, Worcester, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Cecconi, Francesco" sort="Cecconi, Francesco" uniqKey="Cecconi F" first="Francesco" last="Cecconi">Francesco Cecconi</name>
<affiliation>
<mods:affiliation>Cell Stress and Survival Unit, Danish Cancer Society Research Center, Copenhagen, Denmark</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>IRCCS Fondazione Santa Lucia and Department of Biology, University of Rome Tor Vergata, Rome, Italy</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Codogno, Patrice" sort="Codogno, Patrice" uniqKey="Codogno P" first="Patrice" last="Codogno">Patrice Codogno</name>
<affiliation>
<mods:affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Institut Necker Enfants‐Malades (INEM), Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>INSERM, U1151, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>CNRS, UMR8253, Paris, France</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Debnath, Jayanta" sort="Debnath, Jayanta" uniqKey="Debnath J" first="Jayanta" last="Debnath">Jayanta Debnath</name>
<affiliation>
<mods:affiliation>Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA, San Francisco, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Gewirtz, David A" sort="Gewirtz, David A" uniqKey="Gewirtz D" first="David A" last="Gewirtz">David A. Gewirtz</name>
<affiliation>
<mods:affiliation>Department of Pharmacology, Toxicology and Medicine, Virginia Commonwealth University, VA, RichmondVirginia, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Karantza, Vassiliki" sort="Karantza, Vassiliki" uniqKey="Karantza V" first="Vassiliki" last="Karantza">Vassiliki Karantza</name>
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<mods:affiliation>Merck Research Laboratories, NJ, Rahway, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kimmelman, Alec" sort="Kimmelman, Alec" uniqKey="Kimmelman A" first="Alec" last="Kimmelman">Alec Kimmelman</name>
<affiliation>
<mods:affiliation>Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana‐Farber Cancer Institute, MA, Boston, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kumar, Sharad" sort="Kumar, Sharad" uniqKey="Kumar S" first="Sharad" last="Kumar">Sharad Kumar</name>
<affiliation>
<mods:affiliation>Centre for Cancer Biology, University of South Australia, SA, Adelaide, Australia</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Levine, Beth" sort="Levine, Beth" uniqKey="Levine B" first="Beth" last="Levine">Beth Levine</name>
<affiliation>
<mods:affiliation>Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, TX, Dallas, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Maiuri, Maria Chiara" sort="Maiuri, Maria Chiara" uniqKey="Maiuri M" first="Maria Chiara" last="Maiuri">Maria Chiara Maiuri</name>
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<mods:affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>INSERM, U1138, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Gustave Roussy Cancer Campus, Villejuif, France</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Martin, Seamus J" sort="Martin, Seamus J" uniqKey="Martin S" first="Seamus J" last="Martin">Seamus J. Martin</name>
<affiliation>
<mods:affiliation>Department of Genetics, Trinity College, The Smurfit Institute, Dublin, Ireland</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Penninger, Josef" sort="Penninger, Josef" uniqKey="Penninger J" first="Josef" last="Penninger">Josef Penninger</name>
<affiliation>
<mods:affiliation>Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Piacentini, Mauro" sort="Piacentini, Mauro" uniqKey="Piacentini M" first="Mauro" last="Piacentini">Mauro Piacentini</name>
<affiliation>
<mods:affiliation>Department of Biology, University of Rome Tor Vergata, Rome, Italy</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Rubinsztein, David C" sort="Rubinsztein, David C" uniqKey="Rubinsztein D" first="David C" last="Rubinsztein">David C. Rubinsztein</name>
<affiliation>
<mods:affiliation>Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Simon, Hans We" sort="Simon, Hans We" uniqKey="Simon H" first="Hans-Uwe" last="Simon">Hans-Uwe Simon</name>
<affiliation>
<mods:affiliation>Institute of Pharmacology, University of Bern, Bern, Switzerland</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Simonsen, Anne" sort="Simonsen, Anne" uniqKey="Simonsen A" first="Anne" last="Simonsen">Anne Simonsen</name>
<affiliation>
<mods:affiliation>Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Thorburn, Andrew M" sort="Thorburn, Andrew M" uniqKey="Thorburn A" first="Andrew M" last="Thorburn">Andrew M. Thorburn</name>
<affiliation>
<mods:affiliation>Department of Pharmacology, University of Colorado School of Medicine, CO, Aurora, USA</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Velasco, Guillermo" sort="Velasco, Guillermo" uniqKey="Velasco G" first="Guillermo" last="Velasco">Guillermo Velasco</name>
<affiliation>
<mods:affiliation>Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University of Madrid, Madrid, Spain</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Ryan, Kevin M" sort="Ryan, Kevin M" uniqKey="Ryan K" first="Kevin M" last="Ryan">Kevin M. Ryan</name>
<affiliation>
<mods:affiliation>Cancer Research UK Beatson Institute, Glasgow, UK</mods:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kroemer, Guido" sort="Kroemer, Guido" uniqKey="Kroemer G" first="Guido" last="Kroemer">Guido Kroemer</name>
<affiliation>
<mods:affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>INSERM, U1138, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP‐HP, Paris, France</mods:affiliation>
</affiliation>
<affiliation>
<mods:affiliation>Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France</mods:affiliation>
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<title level="j" type="main">The EMBO Journal</title>
<title level="j" type="alt">THE EMBO JOURNAL</title>
<idno type="ISSN">0261-4189</idno>
<idno type="eISSN">1460-2075</idno>
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<div type="abstract">Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.</div>
<div type="abstract" xml:lang="en">Autophagy has been described to have tumor‐suppressive as well as tumor‐promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy.</div>
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<name>José Manuel Bravo‐San Pedro</name>
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<p>Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.</p>
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<p>Autophagy has been described to have tumor‐suppressive as well as tumor‐promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy.
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<p>Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.</p>
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<p>Autophagy has been described to have tumor‐suppressive as well as tumor‐promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy.
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<note type="equal" xml:id="embj201490784-note-0001">These authors contributed equally to this work</note>
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<title>Autophagy in malignant transformation and cancer progression</title>
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<title>Autophagy in malignant transformation and cancer progression</title>
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<name type="personal">
<namePart type="given">Lorenzo</namePart>
<namePart type="family">Galluzzi</namePart>
<affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</affiliation>
<affiliation>INSERM, U1138, Paris, France</affiliation>
<affiliation>Gustave Roussy Cancer Campus, Villejuif, France</affiliation>
<affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</affiliation>
<description>Note: These authors contributed equally to this work</description>
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<affiliation>E-mail: deadoc@vodafone.it</affiliation>
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<affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</affiliation>
<affiliation>INSERM, U1138, Paris, France</affiliation>
<affiliation>Gustave Roussy Cancer Campus, Villejuif, France</affiliation>
<description>These authors contributed equally to this work</description>
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<namePart type="given">José Manuel</namePart>
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<affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</affiliation>
<affiliation>INSERM, U1138, Paris, France</affiliation>
<affiliation>Gustave Roussy Cancer Campus, Villejuif, France</affiliation>
<description>These authors contributed equally to this work</description>
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<namePart type="given">Eric H</namePart>
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<affiliation>Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, MA, Worcester, USA</affiliation>
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<namePart type="given">Francesco</namePart>
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<affiliation>IRCCS Fondazione Santa Lucia and Department of Biology, University of Rome Tor Vergata, Rome, Italy</affiliation>
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<affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</affiliation>
<affiliation>Institut Necker Enfants‐Malades (INEM), Paris, France</affiliation>
<affiliation>INSERM, U1151, Paris, France</affiliation>
<affiliation>CNRS, UMR8253, Paris, France</affiliation>
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<affiliation>Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA, San Francisco, USA</affiliation>
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<name type="personal">
<namePart type="given">David A</namePart>
<namePart type="family">Gewirtz</namePart>
<affiliation>Department of Pharmacology, Toxicology and Medicine, Virginia Commonwealth University, VA, RichmondVirginia, USA</affiliation>
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<namePart type="given">Vassiliki</namePart>
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<affiliation>Merck Research Laboratories, NJ, Rahway, USA</affiliation>
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<namePart type="given">Alec</namePart>
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<affiliation>Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana‐Farber Cancer Institute, MA, Boston, USA</affiliation>
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<namePart type="family">Kumar</namePart>
<affiliation>Centre for Cancer Biology, University of South Australia, SA, Adelaide, Australia</affiliation>
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<name type="personal">
<namePart type="given">Beth</namePart>
<namePart type="family">Levine</namePart>
<affiliation>Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA</affiliation>
<affiliation>Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA</affiliation>
<affiliation>Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, TX, Dallas, USA</affiliation>
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<namePart type="given">Maria Chiara</namePart>
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<affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</affiliation>
<affiliation>INSERM, U1138, Paris, France</affiliation>
<affiliation>Gustave Roussy Cancer Campus, Villejuif, France</affiliation>
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<name type="personal">
<namePart type="given">Seamus J</namePart>
<namePart type="family">Martin</namePart>
<affiliation>Department of Genetics, Trinity College, The Smurfit Institute, Dublin, Ireland</affiliation>
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<namePart type="given">Josef</namePart>
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<namePart type="given">Mauro</namePart>
<namePart type="family">Piacentini</namePart>
<affiliation>Department of Biology, University of Rome Tor Vergata, Rome, Italy</affiliation>
<affiliation>National Institute for Infectious Diseases IRCCS ‘Lazzaro Spallanzani’, Rome, Italy</affiliation>
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<namePart type="given">David C</namePart>
<namePart type="family">Rubinsztein</namePart>
<affiliation>Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK</affiliation>
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<namePart type="given">Hans‐Uwe</namePart>
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<affiliation>Institute of Pharmacology, University of Bern, Bern, Switzerland</affiliation>
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<namePart type="given">Anne</namePart>
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<affiliation>Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway</affiliation>
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<namePart type="given">Andrew M</namePart>
<namePart type="family">Thorburn</namePart>
<affiliation>Department of Pharmacology, University of Colorado School of Medicine, CO, Aurora, USA</affiliation>
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<namePart type="given">Guillermo</namePart>
<namePart type="family">Velasco</namePart>
<affiliation>Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University of Madrid, Madrid, Spain</affiliation>
<affiliation>Instituto de Investigaciones Sanitarias San Carlos (IdISSC), Madrid, Spain</affiliation>
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<affiliation>Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France</affiliation>
<affiliation>INSERM, U1138, Paris, France</affiliation>
<affiliation>Université Paris Descartes, Sorbonne Paris Cité, Paris, France</affiliation>
<affiliation>Pôle de Biologie, Hôpital Européen Georges Pompidou, AP‐HP, Paris, France</affiliation>
<affiliation>Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France</affiliation>
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<abstract>Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.</abstract>
<abstract type="graphical" lang="en">Autophagy has been described to have tumor‐suppressive as well as tumor‐promoting functions. This review discusses how stage and context alters the role for autophagy in cancer, and argues for further research prior to targeting autophagy in cancer therapy.</abstract>
<note type="funding">Agence National de la Recherche (ANR)</note>
<note type="funding">Association pour la recherche sur le cancer (ARC)</note>
<note type="funding">Cancéropôle Ile‐de‐France</note>
<note type="funding">Institut National du Cancer (INCa)</note>
<note type="funding">Fondation Bettencourt‐Schueller</note>
<note type="funding">Fondation de France</note>
<note type="funding">Fondation pour la Recherche Médicale (FRM)</note>
<note type="funding">European Commission (ArtForce)</note>
<note type="funding">European Research Council (ERC)</note>
<note type="funding">LabEx Immuno‐Oncology</note>
<note type="funding">SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)</note>
<note type="funding">SIRIC Cancer Research and Personalized Medicine (CARPEM)</note>
<note type="funding">Paris Alliance of Cancer Research Institutes (PACRI)</note>
<note type="funding">American Cancer Society</note>
<note type="funding">Institutional Research Grant - No. IRG‐14‐192‐40; </note>
<note type="funding">National Health and Medical Research Council of Australia Project Grant - No. 1041807; </note>
<note type="funding">Senior Principal Research Fellowship - No. 1002863; </note>
<note type="funding">Ministry of Health of Italy (‘Ricerca Corrente’ and ‘Ricerca Finalizzata’)</note>
<note type="funding">Associazione Italiana per la Ricerca sul Cancro (AIRC)</note>
<note type="funding">Swiss National Science Foundation</note>
<note type="funding">Swiss Cancer League</note>
<note type="funding">European Commission (MEL‐PLEX)</note>
<note type="funding">Spanish Ministry of Economy and Competitiveness (MINECO)</note>
<note type="funding">Fondo Europeo de Desarrollo Regional (FEDER) - No. PI12/02248; No. FR2009‐0052; No. IT2009‐0053; </note>
<note type="funding">Fundación Mutua Madrileña - No. AP101042012; </note>
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