Induction of dormancy in hypoxic human papillomavirus-positive cancer cells.
Identifieur interne : 000812 ( Main/Exploration ); précédent : 000811; suivant : 000813Induction of dormancy in hypoxic human papillomavirus-positive cancer cells.
Auteurs : Karin Hoppe-Seyler [Allemagne] ; Felicitas Bossler [Allemagne] ; Claudia Lohrey [Allemagne] ; Julia Bulkescher [Allemagne] ; Frank Rösl [Allemagne] ; Lars Jansen [Allemagne] ; Arnulf Mayer [Allemagne] ; Peter Vaupel [Allemagne] ; Matthias Dürst [Allemagne] ; Felix Hoppe-Seyler [Allemagne]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 2017.
Descripteurs français
- KwdFr :
- Cellules HCT116 (MeSH), Cellules HeLa (MeSH), Cellules HepG2 (MeSH), Cellules MCF-7 (MeSH), Femelle (MeSH), Humains (MeSH), Hypoxie (MeSH), Hypoxie cellulaire (MeSH), Interactions hôte-pathogène (génétique), Lignée cellulaire (MeSH), Lignée cellulaire tumorale (MeSH), Papillomaviridae (génétique), Papillomaviridae (métabolisme), Papillomaviridae (physiologie), Protéine p53 suppresseur de tumeur (génétique), Protéine p53 suppresseur de tumeur (métabolisme), Protéines E7 de papillomavirus (génétique), Protéines E7 de papillomavirus (métabolisme), Protéines de répression (génétique), Protéines de répression (métabolisme), Protéines des oncogènes viraux (génétique), Protéines des oncogènes viraux (métabolisme), Régulation de l'expression des gènes tumoraux (MeSH), Régulation de l'expression des gènes viraux (MeSH), Tumeurs (génétique), Tumeurs (métabolisme), Tumeurs (virologie), Tumeurs du col de l'utérus (génétique), Tumeurs du col de l'utérus (métabolisme), Tumeurs du col de l'utérus (virologie), Vieillissement de la cellule (génétique).
- MESH :
- génétique : Interactions hôte-pathogène, Papillomaviridae, Protéine p53 suppresseur de tumeur, Protéines E7 de papillomavirus, Protéines de répression, Protéines des oncogènes viraux, Tumeurs, Tumeurs du col de l'utérus, Vieillissement de la cellule.
- métabolisme : Papillomaviridae, Protéine p53 suppresseur de tumeur, Protéines E7 de papillomavirus, Protéines de répression, Protéines des oncogènes viraux, Tumeurs, Tumeurs du col de l'utérus.
- physiologie : Papillomaviridae.
- virologie : Tumeurs, Tumeurs du col de l'utérus.
- Cellules HCT116, Cellules HeLa, Cellules HepG2, Cellules MCF-7, Femelle, Humains, Hypoxie, Hypoxie cellulaire, Lignée cellulaire, Lignée cellulaire tumorale, Régulation de l'expression des gènes tumoraux, Régulation de l'expression des gènes viraux.
English descriptors
- KwdEn :
- Cell Hypoxia (MeSH), Cell Line (MeSH), Cell Line, Tumor (MeSH), Cellular Senescence (genetics), Female (MeSH), Gene Expression Regulation, Neoplastic (MeSH), Gene Expression Regulation, Viral (MeSH), HCT116 Cells (MeSH), HeLa Cells (MeSH), Hep G2 Cells (MeSH), Host-Pathogen Interactions (genetics), Humans (MeSH), Hypoxia (MeSH), MCF-7 Cells (MeSH), Neoplasms (genetics), Neoplasms (metabolism), Neoplasms (virology), Oncogene Proteins, Viral (genetics), Oncogene Proteins, Viral (metabolism), Papillomaviridae (genetics), Papillomaviridae (metabolism), Papillomaviridae (physiology), Papillomavirus E7 Proteins (genetics), Papillomavirus E7 Proteins (metabolism), Repressor Proteins (genetics), Repressor Proteins (metabolism), Tumor Suppressor Protein p53 (genetics), Tumor Suppressor Protein p53 (metabolism), Uterine Cervical Neoplasms (genetics), Uterine Cervical Neoplasms (metabolism), Uterine Cervical Neoplasms (virology).
- MESH :
- chemical , genetics : Oncogene Proteins, Viral, Papillomavirus E7 Proteins, Repressor Proteins, Tumor Suppressor Protein p53.
- genetics : Cellular Senescence, Host-Pathogen Interactions, Neoplasms, Papillomaviridae, Uterine Cervical Neoplasms.
- metabolism : Neoplasms, Oncogene Proteins, Viral, Papillomaviridae, Papillomavirus E7 Proteins, Repressor Proteins, Tumor Suppressor Protein p53, Uterine Cervical Neoplasms.
- physiology : Papillomaviridae.
- virology : Neoplasms, Uterine Cervical Neoplasms.
- Cell Hypoxia, Cell Line, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, Viral, HCT116 Cells, HeLa Cells, Hep G2 Cells, Humans, Hypoxia, MCF-7 Cells.
Abstract
Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation.
DOI: 10.1073/pnas.1615758114
PubMed: 28115701
PubMed Central: PMC5307428
Affiliations:
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xml:lang="fr">Allemagne</country><wicri:regionArea>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Bossler, Felicitas" sort="Bossler, Felicitas" uniqKey="Bossler F" first="Felicitas" last="Bossler">Felicitas Bossler</name><affiliation wicri:level="3"><nlm:affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Lohrey, Claudia" sort="Lohrey, Claudia" uniqKey="Lohrey C" first="Claudia" last="Lohrey">Claudia Lohrey</name><affiliation wicri:level="3"><nlm:affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Bulkescher, Julia" sort="Bulkescher, Julia" uniqKey="Bulkescher J" first="Julia" last="Bulkescher">Julia Bulkescher</name><affiliation wicri:level="3"><nlm:affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Rosl, Frank" sort="Rosl, Frank" uniqKey="Rosl F" first="Frank" last="Rösl">Frank Rösl</name><affiliation wicri:level="3"><nlm:affiliation>Viral Transformation Mechanisms (F030), German Cancer Research Center, D-69120 Heidelberg, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Viral Transformation Mechanisms (F030), German Cancer Research Center, D-69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author><author><name sortKey="Jansen, Lars" sort="Jansen, Lars" uniqKey="Jansen L" first="Lars" last="Jansen">Lars Jansen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynecology, Jena University Hospital, D-07743 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Gynecology, Jena University Hospital, D-07743 Jena</wicri:regionArea><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>D-07743 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Mayer, Arnulf" sort="Mayer, Arnulf" uniqKey="Mayer A" first="Arnulf" last="Mayer">Arnulf Mayer</name><affiliation wicri:level="3"><nlm:affiliation>Department of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz</wicri:regionArea><placeName><region type="land" nuts="2">Rhénanie-Palatinat</region><settlement type="city">Mayence</settlement></placeName></affiliation></author><author><name sortKey="Vaupel, Peter" sort="Vaupel, Peter" uniqKey="Vaupel P" first="Peter" last="Vaupel">Peter Vaupel</name><affiliation wicri:level="3"><nlm:affiliation>Department of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz</wicri:regionArea><placeName><region type="land" nuts="2">Rhénanie-Palatinat</region><settlement type="city">Mayence</settlement></placeName></affiliation></author><author><name sortKey="Durst, Matthias" sort="Durst, Matthias" uniqKey="Durst M" first="Matthias" last="Dürst">Matthias Dürst</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gynecology, Jena University Hospital, D-07743 Jena, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Gynecology, Jena University Hospital, D-07743 Jena</wicri:regionArea><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>07743 Jena</wicri:noRegion><wicri:noRegion>D-07743 Jena</wicri:noRegion></affiliation></author><author><name sortKey="Hoppe Seyler, Felix" sort="Hoppe Seyler, Felix" uniqKey="Hoppe Seyler F" first="Felix" last="Hoppe-Seyler">Felix Hoppe-Seyler</name><affiliation wicri:level="3"><nlm:affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany; hoppe-seyler@dkfz.de.</nlm:affiliation><country wicri:rule="url">Allemagne</country><wicri:regionArea>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Karlsruhe</region><settlement type="city">Heidelberg</settlement></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Hypoxia (MeSH)</term><term>Cell Line (MeSH)</term><term>Cell Line, Tumor (MeSH)</term><term>Cellular Senescence (genetics)</term><term>Female (MeSH)</term><term>Gene Expression Regulation, Neoplastic (MeSH)</term><term>Gene Expression Regulation, Viral (MeSH)</term><term>HCT116 Cells (MeSH)</term><term>HeLa Cells (MeSH)</term><term>Hep G2 Cells (MeSH)</term><term>Host-Pathogen Interactions (genetics)</term><term>Humans (MeSH)</term><term>Hypoxia (MeSH)</term><term>MCF-7 Cells (MeSH)</term><term>Neoplasms (genetics)</term><term>Neoplasms (metabolism)</term><term>Neoplasms (virology)</term><term>Oncogene Proteins, Viral (genetics)</term><term>Oncogene Proteins, Viral (metabolism)</term><term>Papillomaviridae (genetics)</term><term>Papillomaviridae (metabolism)</term><term>Papillomaviridae (physiology)</term><term>Papillomavirus E7 Proteins (genetics)</term><term>Papillomavirus E7 Proteins (metabolism)</term><term>Repressor Proteins (genetics)</term><term>Repressor Proteins (metabolism)</term><term>Tumor Suppressor Protein p53 (genetics)</term><term>Tumor Suppressor Protein p53 (metabolism)</term><term>Uterine Cervical Neoplasms (genetics)</term><term>Uterine Cervical Neoplasms (metabolism)</term><term>Uterine Cervical Neoplasms (virology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cellules HCT116 (MeSH)</term><term>Cellules HeLa (MeSH)</term><term>Cellules HepG2 (MeSH)</term><term>Cellules MCF-7 (MeSH)</term><term>Femelle (MeSH)</term><term>Humains (MeSH)</term><term>Hypoxie (MeSH)</term><term>Hypoxie cellulaire (MeSH)</term><term>Interactions hôte-pathogène (génétique)</term><term>Lignée cellulaire (MeSH)</term><term>Lignée cellulaire tumorale (MeSH)</term><term>Papillomaviridae (génétique)</term><term>Papillomaviridae (métabolisme)</term><term>Papillomaviridae (physiologie)</term><term>Protéine p53 suppresseur de tumeur (génétique)</term><term>Protéine p53 suppresseur de tumeur (métabolisme)</term><term>Protéines E7 de papillomavirus (génétique)</term><term>Protéines E7 de papillomavirus (métabolisme)</term><term>Protéines de répression (génétique)</term><term>Protéines de répression (métabolisme)</term><term>Protéines des oncogènes viraux (génétique)</term><term>Protéines des oncogènes viraux (métabolisme)</term><term>Régulation de l'expression des gènes tumoraux (MeSH)</term><term>Régulation de l'expression des gènes viraux (MeSH)</term><term>Tumeurs (génétique)</term><term>Tumeurs (métabolisme)</term><term>Tumeurs (virologie)</term><term>Tumeurs du col de l'utérus (génétique)</term><term>Tumeurs du col de l'utérus (métabolisme)</term><term>Tumeurs du col de l'utérus (virologie)</term><term>Vieillissement de la cellule (génétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Oncogene Proteins, Viral</term><term>Papillomavirus E7 Proteins</term><term>Repressor Proteins</term><term>Tumor Suppressor Protein p53</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cellular Senescence</term><term>Host-Pathogen Interactions</term><term>Neoplasms</term><term>Papillomaviridae</term><term>Uterine Cervical Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Interactions hôte-pathogène</term><term>Papillomaviridae</term><term>Protéine p53 suppresseur de tumeur</term><term>Protéines E7 de papillomavirus</term><term>Protéines de répression</term><term>Protéines des oncogènes viraux</term><term>Tumeurs</term><term>Tumeurs du col de l'utérus</term><term>Vieillissement de la cellule</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neoplasms</term><term>Oncogene Proteins, Viral</term><term>Papillomaviridae</term><term>Papillomavirus E7 Proteins</term><term>Repressor Proteins</term><term>Tumor Suppressor Protein p53</term><term>Uterine Cervical Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Papillomaviridae</term><term>Protéine p53 suppresseur de tumeur</term><term>Protéines E7 de papillomavirus</term><term>Protéines de répression</term><term>Protéines des oncogènes viraux</term><term>Tumeurs</term><term>Tumeurs du col de l'utérus</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Papillomaviridae</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Papillomaviridae</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Tumeurs</term><term>Tumeurs du col de l'utérus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Neoplasms</term><term>Uterine Cervical Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Hypoxia</term><term>Cell Line</term><term>Cell Line, Tumor</term><term>Female</term><term>Gene Expression Regulation, Neoplastic</term><term>Gene Expression Regulation, Viral</term><term>HCT116 Cells</term><term>HeLa Cells</term><term>Hep G2 Cells</term><term>Humans</term><term>Hypoxia</term><term>MCF-7 Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules HCT116</term><term>Cellules HeLa</term><term>Cellules HepG2</term><term>Cellules MCF-7</term><term>Femelle</term><term>Humains</term><term>Hypoxie</term><term>Hypoxie cellulaire</term><term>Lignée cellulaire</term><term>Lignée cellulaire tumorale</term><term>Régulation de l'expression des gènes tumoraux</term><term>Régulation de l'expression des gènes viraux</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28115701</PMID><DateCompleted><Year>2018</Year><Month>04</Month><Day>16</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1091-6490</ISSN><JournalIssue CitedMedium="Internet"><Volume>114</Volume><Issue>6</Issue><PubDate><Year>2017</Year><Month>02</Month><Day>07</Day></PubDate></JournalIssue><Title>Proceedings of the National Academy of Sciences of the United States of America</Title><ISOAbbreviation>Proc Natl Acad Sci U S A</ISOAbbreviation></Journal><ArticleTitle>Induction of dormancy in hypoxic human papillomavirus-positive cancer cells.</ArticleTitle><Pagination><MedlinePgn>E990-E998</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1073/pnas.1615758114</ELocationID><Abstract><AbstractText>Oncogenic human papillomaviruses (HPVs) are closely linked to major human malignancies, including cervical and head and neck cancers. It is widely assumed that HPV-positive cancer cells are under selection pressure to continuously express the viral E6/E7 oncogenes, that their intracellular p53 levels are reconstituted on E6/E7 repression, and that E6/E7 inhibition phenotypically results in cellular senescence. Here we show that hypoxic conditions, as are often found in subregions of cervical and head and neck cancers, enable HPV-positive cancer cells to escape from these regulatory principles: E6/E7 is efficiently repressed, yet, p53 levels do not increase. Moreover, E6/E7 repression under hypoxia does not result in cellular senescence, owing to hypoxia-associated impaired mechanistic target of rapamycin (mTOR) signaling via the inhibitory REDD1/TSC2 axis. Instead, a reversible growth arrest is induced that can be overcome by reoxygenation. Impairment of mTOR signaling also interfered with the senescence response of hypoxic HPV-positive cancer cells toward prosenescent chemotherapy in vitro. Collectively, these findings indicate that hypoxic HPV-positive cancer cells can induce a reversible state of dormancy, with decreased viral antigen synthesis and increased therapeutic resistance, and may serve as reservoirs for tumor recurrence on reoxygenation.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hoppe-Seyler</LastName><ForeName>Karin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bossler</LastName><ForeName>Felicitas</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lohrey</LastName><ForeName>Claudia</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bulkescher</LastName><ForeName>Julia</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rösl</LastName><ForeName>Frank</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Viral Transformation Mechanisms (F030), German Cancer Research Center, D-69120 Heidelberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jansen</LastName><ForeName>Lars</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Gynecology, Jena University Hospital, D-07743 Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mayer</LastName><ForeName>Arnulf</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vaupel</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Radiooncology and Radiotherapy, Mainz University Medical Center, D-55131 Mainz, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dürst</LastName><ForeName>Matthias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Gynecology, Jena University Hospital, D-07743 Jena, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoppe-Seyler</LastName><ForeName>Felix</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Molecular Therapy of Virus-Associated Cancers (F065), German Cancer Research Center, D-69120 Heidelberg, Germany; hoppe-seyler@dkfz.de.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>01</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Proc Natl Acad Sci U S A</MedlineTA><NlmUniqueID>7505876</NlmUniqueID><ISSNLinking>0027-8424</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C068651">E6 protein, Human papillomavirus type 16</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009856">Oncogene Proteins, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050725">Papillomavirus E7 Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012097">Repressor Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016159">Tumor Suppressor Protein p53</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C059731">oncogene protein E7, Human papillomavirus type 16</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>Front Oncol. 2018 Mar 27;8:77</RefSource><PMID Version="1">29637045</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D015687" MajorTopicYN="N">Cell Hypoxia</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016922" MajorTopicYN="N">Cellular Senescence</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015972" MajorTopicYN="Y">Gene Expression Regulation, Neoplastic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015967" MajorTopicYN="Y">Gene Expression Regulation, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045325" MajorTopicYN="N">HCT116 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006367" MajorTopicYN="N">HeLa Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056945" MajorTopicYN="N">Hep G2 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054884" MajorTopicYN="N">Host-Pathogen Interactions</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000860" MajorTopicYN="N">Hypoxia</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D061986" MajorTopicYN="N">MCF-7 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009369" MajorTopicYN="N">Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009856" MajorTopicYN="N">Oncogene Proteins, Viral</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D027383" MajorTopicYN="N">Papillomaviridae</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050725" MajorTopicYN="N">Papillomavirus E7 Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012097" MajorTopicYN="N">Repressor Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016159" MajorTopicYN="N">Tumor Suppressor Protein p53</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002583" MajorTopicYN="N">Uterine Cervical Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">cervical cancer</Keyword><Keyword MajorTopicYN="Y">human papillomavirus</Keyword><Keyword MajorTopicYN="Y">hypoxia</Keyword><Keyword MajorTopicYN="Y">mTOR</Keyword><Keyword MajorTopicYN="Y">tumor virus</Keyword></KeywordList><CoiStatement>The authors declare no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate 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Bossler</name><name sortKey="Bulkescher, Julia" sort="Bulkescher, Julia" uniqKey="Bulkescher J" first="Julia" last="Bulkescher">Julia Bulkescher</name><name sortKey="Durst, Matthias" sort="Durst, Matthias" uniqKey="Durst M" first="Matthias" last="Dürst">Matthias Dürst</name><name sortKey="Hoppe Seyler, Felix" sort="Hoppe Seyler, Felix" uniqKey="Hoppe Seyler F" first="Felix" last="Hoppe-Seyler">Felix Hoppe-Seyler</name><name sortKey="Jansen, Lars" sort="Jansen, Lars" uniqKey="Jansen L" first="Lars" last="Jansen">Lars Jansen</name><name sortKey="Lohrey, Claudia" sort="Lohrey, Claudia" uniqKey="Lohrey C" first="Claudia" last="Lohrey">Claudia Lohrey</name><name sortKey="Mayer, Arnulf" sort="Mayer, Arnulf" uniqKey="Mayer A" first="Arnulf" last="Mayer">Arnulf Mayer</name><name sortKey="Rosl, Frank" sort="Rosl, Frank" uniqKey="Rosl F" first="Frank" last="Rösl">Frank Rösl</name><name sortKey="Vaupel, Peter" sort="Vaupel, Peter" uniqKey="Vaupel P" first="Peter" last="Vaupel">Peter 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