Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression.
Identifieur interne : 000240 ( France/Analysis ); précédent : 000239; suivant : 000241Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression.
Auteurs : Muhammad Zaeem Noman [France] ; Bassam Janji ; Bozena Kaminska ; Kris Van Moer ; Sandrine Pierson ; Piotr Przanowski ; Stéphanie Buart ; Guy Berchem ; Pedro Romero ; Fathia Mami-Chouaib ; Salem ChouaibSource :
- Cancer research [ 1538-7445 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux, Autophagie (immunologie), Facteur de transcription STAT-3 (métabolisme), Humains, Hypoxie cellulaire (immunologie), Lignée cellulaire tumorale, Lymphocytes T cytotoxiques (immunologie), Mélanome expérimental (anatomopathologie), Mélanome expérimental (immunologie), Mélanome expérimental (métabolisme), Phosphorylation, Proteasome endopeptidase complex (métabolisme), Protéines adaptatrices de la transduction du signal (métabolisme), Protéines du choc thermique (métabolisme), Souris, Souris de lignée C57BL, Séquestosome-1, Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (immunologie), Tumeurs du poumon (métabolisme), Ubiquitine (métabolisme), src-Family kinases (métabolisme).
- MESH :
- anatomopathologie : Mélanome expérimental, Tumeurs du poumon.
- immunologie : Autophagie, Hypoxie cellulaire, Lymphocytes T cytotoxiques, Mélanome expérimental, Tumeurs du poumon.
- métabolisme : Facteur de transcription STAT-3, Mélanome expérimental, Proteasome endopeptidase complex, Protéines adaptatrices de la transduction du signal, Protéines du choc thermique, Tumeurs du poumon, Ubiquitine, src-Family kinases.
- Animaux, Humains, Lignée cellulaire tumorale, Phosphorylation, Souris, Souris de lignée C57BL, Séquestosome-1.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (metabolism), Animals, Autophagy (immunology), Cell Hypoxia (immunology), Cell Line, Tumor, Heat-Shock Proteins (metabolism), Humans, Lung Neoplasms (immunology), Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Melanoma, Experimental (immunology), Melanoma, Experimental (metabolism), Melanoma, Experimental (pathology), Mice, Mice, Inbred C57BL, Phosphorylation, Proteasome Endopeptidase Complex (metabolism), STAT3 Transcription Factor (metabolism), Sequestosome-1 Protein, T-Lymphocytes, Cytotoxic (immunology), Ubiquitin (metabolism), src-Family Kinases (metabolism).
- MESH :
- chemical , metabolism : Adaptor Proteins, Signal Transducing, Heat-Shock Proteins, Proteasome Endopeptidase Complex, STAT3 Transcription Factor, Ubiquitin, src-Family Kinases.
- immunology : Autophagy, Cell Hypoxia, Lung Neoplasms, Melanoma, Experimental, T-Lymphocytes, Cytotoxic.
- metabolism : Lung Neoplasms, Melanoma, Experimental.
- pathology : Lung Neoplasms, Melanoma, Experimental.
- Animals, Cell Line, Tumor, Humans, Mice, Mice, Inbred C57BL, Phosphorylation, Sequestosome-1 Protein.
Abstract
The relationship between hypoxic stress, autophagy, and specific cell-mediated cytotoxicity remains unknown. This study shows that hypoxia-induced resistance of lung tumor to cytolytic T lymphocyte (CTL)-mediated lysis is associated with autophagy induction in target cells. In turn, this correlates with STAT3 phosphorylation on tyrosine 705 residue (pSTAT3) and HIF-1α accumulation. Inhibition of autophagy by siRNA targeting of either beclin1 or Atg5 resulted in impairment of pSTAT3 and restoration of hypoxic tumor cell susceptibility to CTL-mediated lysis. Furthermore, inhibition of pSTAT3 in hypoxic Atg5 or beclin1-targeted tumor cells was found to be associated with the inhibition Src kinase (pSrc). Autophagy-induced pSTAT3 and pSrc regulation seemed to involve the ubiquitin proteasome system and p62/SQSTM1. In vivo experiments using B16-F10 melanoma tumor cells indicated that depletion of beclin1 resulted in an inhibition of B16-F10 tumor growth and increased tumor apoptosis. Moreover, in vivo inhibition of autophagy by hydroxychloroquine in B16-F10 tumor-bearing mice and mice vaccinated with tyrosinase-related protein-2 peptide dramatically increased tumor growth inhibition. Collectively, this study establishes a novel functional link between hypoxia-induced autophagy and the regulation of antigen-specific T-cell lysis and points to a major role of autophagy in the control of in vivo tumor growth.
DOI: 10.1158/0008-5472.CAN-11-1094
PubMed: 21810913
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000376
- to stream PubMed, to step Curation: 000376
- to stream PubMed, to step Checkpoint: 000373
- to stream Ncbi, to step Merge: 000158
- to stream Ncbi, to step Curation: 000158
- to stream Ncbi, to step Checkpoint: 000158
- to stream Main, to step Merge: 001478
- to stream Main, to step Curation: 001476
- to stream Main, to step Exploration: 001476
- to stream France, to step Extraction: 000240
Links to Exploration step
pubmed:21810913Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression.</title><author><name sortKey="Noman, Muhammad Zaeem" sort="Noman, Muhammad Zaeem" uniqKey="Noman M" first="Muhammad Zaeem" last="Noman">Muhammad Zaeem Noman</name><affiliation wicri:level="1"><nlm:affiliation>Unité INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif Cedex</wicri:regionArea><wicri:noRegion>Villejuif Cedex</wicri:noRegion><wicri:noRegion>Villejuif Cedex</wicri:noRegion></affiliation></author><author><name sortKey="Janji, Bassam" sort="Janji, Bassam" uniqKey="Janji B" first="Bassam" last="Janji">Bassam Janji</name></author><author><name sortKey="Kaminska, Bozena" sort="Kaminska, Bozena" uniqKey="Kaminska B" first="Bozena" last="Kaminska">Bozena Kaminska</name></author><author><name sortKey="Van Moer, Kris" sort="Van Moer, Kris" uniqKey="Van Moer K" first="Kris" last="Van Moer">Kris Van Moer</name></author><author><name sortKey="Pierson, Sandrine" sort="Pierson, Sandrine" uniqKey="Pierson S" first="Sandrine" last="Pierson">Sandrine Pierson</name></author><author><name sortKey="Przanowski, Piotr" sort="Przanowski, Piotr" uniqKey="Przanowski P" first="Piotr" last="Przanowski">Piotr Przanowski</name></author><author><name sortKey="Buart, Stephanie" sort="Buart, Stephanie" uniqKey="Buart S" first="Stéphanie" last="Buart">Stéphanie Buart</name></author><author><name sortKey="Berchem, Guy" sort="Berchem, Guy" uniqKey="Berchem G" first="Guy" last="Berchem">Guy Berchem</name></author><author><name sortKey="Romero, Pedro" sort="Romero, Pedro" uniqKey="Romero P" first="Pedro" last="Romero">Pedro Romero</name></author><author><name sortKey="Mami Chouaib, Fathia" sort="Mami Chouaib, Fathia" uniqKey="Mami Chouaib F" first="Fathia" last="Mami-Chouaib">Fathia Mami-Chouaib</name></author><author><name sortKey="Chouaib, Salem" sort="Chouaib, Salem" uniqKey="Chouaib S" first="Salem" last="Chouaib">Salem Chouaib</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21810913</idno><idno type="pmid">21810913</idno><idno type="doi">10.1158/0008-5472.CAN-11-1094</idno><idno type="wicri:Area/PubMed/Corpus">000376</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000376</idno><idno type="wicri:Area/PubMed/Curation">000376</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000376</idno><idno type="wicri:Area/PubMed/Checkpoint">000373</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000373</idno><idno type="wicri:Area/Ncbi/Merge">000158</idno><idno type="wicri:Area/Ncbi/Curation">000158</idno><idno type="wicri:Area/Ncbi/Checkpoint">000158</idno><idno type="wicri:Area/Main/Merge">001478</idno><idno type="wicri:Area/Main/Curation">001476</idno><idno type="wicri:Area/Main/Exploration">001476</idno><idno type="wicri:Area/France/Extraction">000240</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression.</title><author><name sortKey="Noman, Muhammad Zaeem" sort="Noman, Muhammad Zaeem" uniqKey="Noman M" first="Muhammad Zaeem" last="Noman">Muhammad Zaeem Noman</name><affiliation wicri:level="1"><nlm:affiliation>Unité INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif Cedex, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif Cedex</wicri:regionArea><wicri:noRegion>Villejuif Cedex</wicri:noRegion><wicri:noRegion>Villejuif Cedex</wicri:noRegion></affiliation></author><author><name sortKey="Janji, Bassam" sort="Janji, Bassam" uniqKey="Janji B" first="Bassam" last="Janji">Bassam Janji</name></author><author><name sortKey="Kaminska, Bozena" sort="Kaminska, Bozena" uniqKey="Kaminska B" first="Bozena" last="Kaminska">Bozena Kaminska</name></author><author><name sortKey="Van Moer, Kris" sort="Van Moer, Kris" uniqKey="Van Moer K" first="Kris" last="Van Moer">Kris Van Moer</name></author><author><name sortKey="Pierson, Sandrine" sort="Pierson, Sandrine" uniqKey="Pierson S" first="Sandrine" last="Pierson">Sandrine Pierson</name></author><author><name sortKey="Przanowski, Piotr" sort="Przanowski, Piotr" uniqKey="Przanowski P" first="Piotr" last="Przanowski">Piotr Przanowski</name></author><author><name sortKey="Buart, Stephanie" sort="Buart, Stephanie" uniqKey="Buart S" first="Stéphanie" last="Buart">Stéphanie Buart</name></author><author><name sortKey="Berchem, Guy" sort="Berchem, Guy" uniqKey="Berchem G" first="Guy" last="Berchem">Guy Berchem</name></author><author><name sortKey="Romero, Pedro" sort="Romero, Pedro" uniqKey="Romero P" first="Pedro" last="Romero">Pedro Romero</name></author><author><name sortKey="Mami Chouaib, Fathia" sort="Mami Chouaib, Fathia" uniqKey="Mami Chouaib F" first="Fathia" last="Mami-Chouaib">Fathia Mami-Chouaib</name></author><author><name sortKey="Chouaib, Salem" sort="Chouaib, Salem" uniqKey="Chouaib S" first="Salem" last="Chouaib">Salem Chouaib</name></author></analytic><series><title level="j">Cancer research</title><idno type="eISSN">1538-7445</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adaptor Proteins, Signal Transducing (metabolism)</term><term>Animals</term><term>Autophagy (immunology)</term><term>Cell Hypoxia (immunology)</term><term>Cell Line, Tumor</term><term>Heat-Shock Proteins (metabolism)</term><term>Humans</term><term>Lung Neoplasms (immunology)</term><term>Lung Neoplasms (metabolism)</term><term>Lung Neoplasms (pathology)</term><term>Melanoma, Experimental (immunology)</term><term>Melanoma, Experimental (metabolism)</term><term>Melanoma, Experimental (pathology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Phosphorylation</term><term>Proteasome Endopeptidase Complex (metabolism)</term><term>STAT3 Transcription Factor (metabolism)</term><term>Sequestosome-1 Protein</term><term>T-Lymphocytes, Cytotoxic (immunology)</term><term>Ubiquitin (metabolism)</term><term>src-Family Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Autophagie (immunologie)</term><term>Facteur de transcription STAT-3 (métabolisme)</term><term>Humains</term><term>Hypoxie cellulaire (immunologie)</term><term>Lignée cellulaire tumorale</term><term>Lymphocytes T cytotoxiques (immunologie)</term><term>Mélanome expérimental (anatomopathologie)</term><term>Mélanome expérimental (immunologie)</term><term>Mélanome expérimental (métabolisme)</term><term>Phosphorylation</term><term>Proteasome endopeptidase complex (métabolisme)</term><term>Protéines adaptatrices de la transduction du signal (métabolisme)</term><term>Protéines du choc thermique (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Séquestosome-1</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (immunologie)</term><term>Tumeurs du poumon (métabolisme)</term><term>Ubiquitine (métabolisme)</term><term>src-Family kinases (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adaptor Proteins, Signal Transducing</term><term>Heat-Shock Proteins</term><term>Proteasome Endopeptidase Complex</term><term>STAT3 Transcription Factor</term><term>Ubiquitin</term><term>src-Family Kinases</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Mélanome expérimental</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Autophagie</term><term>Hypoxie cellulaire</term><term>Lymphocytes T cytotoxiques</term><term>Mélanome expérimental</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Autophagy</term><term>Cell Hypoxia</term><term>Lung Neoplasms</term><term>Melanoma, Experimental</term><term>T-Lymphocytes, Cytotoxic</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Neoplasms</term><term>Melanoma, Experimental</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de transcription STAT-3</term><term>Mélanome expérimental</term><term>Proteasome endopeptidase complex</term><term>Protéines adaptatrices de la transduction du signal</term><term>Protéines du choc thermique</term><term>Tumeurs du poumon</term><term>Ubiquitine</term><term>src-Family kinases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term><term>Melanoma, Experimental</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Phosphorylation</term><term>Sequestosome-1 Protein</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Phosphorylation</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Séquestosome-1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The relationship between hypoxic stress, autophagy, and specific cell-mediated cytotoxicity remains unknown. This study shows that hypoxia-induced resistance of lung tumor to cytolytic T lymphocyte (CTL)-mediated lysis is associated with autophagy induction in target cells. In turn, this correlates with STAT3 phosphorylation on tyrosine 705 residue (pSTAT3) and HIF-1α accumulation. Inhibition of autophagy by siRNA targeting of either beclin1 or Atg5 resulted in impairment of pSTAT3 and restoration of hypoxic tumor cell susceptibility to CTL-mediated lysis. Furthermore, inhibition of pSTAT3 in hypoxic Atg5 or beclin1-targeted tumor cells was found to be associated with the inhibition Src kinase (pSrc). Autophagy-induced pSTAT3 and pSrc regulation seemed to involve the ubiquitin proteasome system and p62/SQSTM1. In vivo experiments using B16-F10 melanoma tumor cells indicated that depletion of beclin1 resulted in an inhibition of B16-F10 tumor growth and increased tumor apoptosis. Moreover, in vivo inhibition of autophagy by hydroxychloroquine in B16-F10 tumor-bearing mice and mice vaccinated with tyrosinase-related protein-2 peptide dramatically increased tumor growth inhibition. Collectively, this study establishes a novel functional link between hypoxia-induced autophagy and the regulation of antigen-specific T-cell lysis and points to a major role of autophagy in the control of in vivo tumor growth.</div></front></TEI><affiliations><list><country><li>France</li></country></list><tree><noCountry><name sortKey="Berchem, Guy" sort="Berchem, Guy" uniqKey="Berchem G" first="Guy" last="Berchem">Guy Berchem</name><name sortKey="Buart, Stephanie" sort="Buart, Stephanie" uniqKey="Buart S" first="Stéphanie" last="Buart">Stéphanie Buart</name><name sortKey="Chouaib, Salem" sort="Chouaib, Salem" uniqKey="Chouaib S" first="Salem" last="Chouaib">Salem Chouaib</name><name sortKey="Janji, Bassam" sort="Janji, Bassam" uniqKey="Janji B" first="Bassam" last="Janji">Bassam Janji</name><name sortKey="Kaminska, Bozena" sort="Kaminska, Bozena" uniqKey="Kaminska B" first="Bozena" last="Kaminska">Bozena Kaminska</name><name sortKey="Mami Chouaib, Fathia" sort="Mami Chouaib, Fathia" uniqKey="Mami Chouaib F" first="Fathia" last="Mami-Chouaib">Fathia Mami-Chouaib</name><name sortKey="Pierson, Sandrine" sort="Pierson, Sandrine" uniqKey="Pierson S" first="Sandrine" last="Pierson">Sandrine Pierson</name><name sortKey="Przanowski, Piotr" sort="Przanowski, Piotr" uniqKey="Przanowski P" first="Piotr" last="Przanowski">Piotr Przanowski</name><name sortKey="Romero, Pedro" sort="Romero, Pedro" uniqKey="Romero P" first="Pedro" last="Romero">Pedro Romero</name><name sortKey="Van Moer, Kris" sort="Van Moer, Kris" uniqKey="Van Moer K" first="Kris" last="Van Moer">Kris Van Moer</name></noCountry><country name="France"><noRegion><name sortKey="Noman, Muhammad Zaeem" sort="Noman, Muhammad Zaeem" uniqKey="Noman M" first="Muhammad Zaeem" last="Noman">Muhammad Zaeem Noman</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/France/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000240 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/France/Analysis/biblio.hfd -nk 000240 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= France
|étape= Analysis
|type= RBID
|clé= pubmed:21810913
|texte= Blocking hypoxia-induced autophagy in tumors restores cytotoxic T-cell activity and promotes regression.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/France/Analysis/RBID.i -Sk "pubmed:21810913" \
| HfdSelect -Kh $EXPLOR_AREA/Data/France/Analysis/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |