HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorRABACHINI, Tatiana
dc.contributor.authorBOCCARDO, Enrique
dc.contributor.authorANDRADE, Rubiana
dc.contributor.authorPEREZ, Katia Regina
dc.contributor.authorNONOGAKI, Suely
dc.contributor.authorCUCCOVIA, Iolanda Midea
dc.contributor.authorVILLA, Luisa Lina
dc.date.accessioned2018-07-05T18:02:14Z
dc.date.available2018-07-05T18:02:14Z
dc.date.issued2018
dc.description.abstractBackground: Human Papillomavirus (HPV) infection is the main risk factor for the development and progression of cervical cancer. HPV-16 E6 and E7 expression is essential for induction and maintenance of the transformed phenotype. These oncoproteins interfere with the function of several intracellular proteins, including those controlling the PI3K/AKT/mTOR pathway in which Phospolipase D (PLD) and Phosphatidic acid (PA) play a critical role. Methods: PLD activity was measured in primary human keratinocytes transduced with retroviruses expressing HPV-16 E6, E7 or E7 mutants. The cytostatic effect of rapamycin, a well-known mTOR inhibitor with potential clinical applications, was evaluated in monolayer and organotypic cultures. Results: HPV-16 E7 expression in primary human keratinocytes leads to an increase in PLD expression and activity. Moreover, this activation is dependent on the ability of HPV-16 E7 to induce retinoblastoma protein (pRb) degradation. We also show that cells expressing HPV-16 E7 or silenced for pRb acquire resistance to the antiproliferative effect of rapamycin. Conclusion: This is the first indication that HPV oncoproteins can affect PLD activity. Since PA can interfere with the ability of rapamycin to bind mTOR, the use of combined strategies to target mTOR and PLD activity might be considered to treat HPV-related malignancies.
dc.description.indexMEDLINE
dc.description.sponsorshipLudwig Institute for Cancer Research
dc.description.sponsorshipFundacao de Amparo a pesquisa do Estado de Sao Paulo (FAPESP) [2003/14008-9, 2010/20002-0, 05/59142-2, 2008/03232-1, 2008/57889-1]
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Pesquisa e Desenvolvimento (CNPq) [573799/2008-3, 480552-2011]
dc.identifier.citationBMC CANCER, v.18, article ID 485, 8p, 2018
dc.identifier.doi10.1186/s12885-018-4392-8
dc.identifier.issn1471-2407
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/26920
dc.language.isoeng
dc.publisherBIOMED CENTRAL LTD
dc.relation.ispartofBMC Cancer
dc.rightsopenAccess
dc.rights.holderCopyright BIOMED CENTRAL LTD
dc.subjectHPV
dc.subjectE7
dc.subjectPLD
dc.subjectPhospholipase
dc.subjectRapamycin
dc.subjectPhosphatidic acid
dc.subjectPA
dc.subjectmTOR
dc.subjectpRb
dc.subject.otherhuman-papillomavirus type-16
dc.subject.othercervical-cancer worldwide
dc.subject.othernecrosis-factor-alpha
dc.subject.otherhuman keratinocytes
dc.subject.otherphosphatidic-acid
dc.subject.otherretinoblastoma protein
dc.subject.othersignaling pathway
dc.subject.othertnf-alpha
dc.subject.otheroncoprotein
dc.subject.othermtor
dc.subject.wosOncology
dc.titleHPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.author.externalRABACHINI, Tatiana:Hosp Sirio Libanes, Ludwig Inst Canc Res, Sao Paulo, SP, Brazil
hcfmusp.author.externalBOCCARDO, Enrique:Hosp Sirio Libanes, Ludwig Inst Canc Res, Sao Paulo, SP, Brazil; Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo, SP, Brazil
hcfmusp.author.externalANDRADE, Rubiana:Univ Sao Paulo, Dept Microbiol, Inst Ciencias Biomed, Sao Paulo, SP, Brazil
hcfmusp.author.externalPEREZ, Katia Regina:Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, SP, Brazil; Univ Fed Sao Paulo, Escola Paulista Med, Dept Biofis, Sao Paulo, SP, Brazil
hcfmusp.author.externalNONOGAKI, Suely:Adolfo Lutz Inst, Ctr Patol, Sao Paulo, SP, Brazil
hcfmusp.author.externalCUCCOVIA, Iolanda Midea:Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo, SP, Brazil
hcfmusp.citation.scopus16
hcfmusp.contributor.author-fmusphcLUISA LINA VILLA
hcfmusp.description.articlenumber485
hcfmusp.description.volume18
hcfmusp.origemWOS
hcfmusp.origem.pubmed29703186
hcfmusp.origem.scopus2-s2.0-85046164189
hcfmusp.origem.wosWOS:000431267000015
hcfmusp.publisher.cityLONDON
hcfmusp.publisher.countryENGLAND
hcfmusp.relation.referenceBasile JR, 2001, J BIOL CHEM, V276, P22522, DOI 10.1074/jbc.M010505200
hcfmusp.relation.referenceBLANTON RA, 1991, AM J PATHOL, V138, P673
hcfmusp.relation.referenceBoccardo E, 2004, VIROLOGY, V328, P233, DOI 10.1016/j.virol.2004.07.026
hcfmusp.relation.referenceBoccardo E, 2010, CARCINOGENESIS, V31, P521, DOI 10.1093/carcin/bgp333
hcfmusp.relation.referenceBoyer SN, 1996, CANCER RES, V56, P4620
hcfmusp.relation.referenceBuchkovich NJ, 2008, NAT REV MICROBIOL, V6, P265, DOI 10.1038/nrmicro1855
hcfmusp.relation.referenceChen YH, 2003, ONCOGENE, V22, P3937, DOI 10.1038/sj.onc.1206565
hcfmusp.relation.referenceClifford GM, 2003, BRIT J CANCER, V88, P63, DOI 10.1038/sj.bjc.6600688
hcfmusp.relation.referenceCoppock JD, 2016, ONCOTARGET, V7, P24228, DOI 10.18632/oncotarget.8286
hcfmusp.relation.referenceD'Souza G, 2007, NEW ENGL J MED, V356, P1944, DOI 10.1056/NEJMoa065497
hcfmusp.relation.referenceDemers GW, 1996, J VIROL, V70, P6862
hcfmusp.relation.referenceFang YM, 2001, SCIENCE, V294, P1942, DOI 10.1126/science.1066015
hcfmusp.relation.referenceFoster DA, 2003, MOL CANCER RES, V1, P789
hcfmusp.relation.referenceFoster DA, 2007, CANCER RES, V67, P1, DOI 10.1158/0008-5472.CAN-06-3016
hcfmusp.relation.referenceGillison ML, 2008, J NATL CANCER I, V100, P407, DOI 10.1093/jnci/djn025
hcfmusp.relation.referenceHAWLEYNELSON P, 1989, EMBO J, V8, P3905
hcfmusp.relation.referenceHebner CM, 2006, REV MED VIROL, V16, P83, DOI 10.1002/rmv.488
hcfmusp.relation.referenceHelt AM, 2003, CARCINOGENESIS, V24, P159, DOI 10.1093/carcin/24.2.159
hcfmusp.relation.referenceHelt AM, 2001, J VIROL, V75, P6737, DOI 10.1128/JVI.75.15.6737-6747.2001
hcfmusp.relation.referenceHidalgo M, 2000, ONCOGENE, V19, P6680, DOI 10.1038/sj.onc.1204091
hcfmusp.relation.referenceJung EM, 1999, CARCINOGENESIS, V20, P569, DOI 10.1093/carcin/20.4.569
hcfmusp.relation.referenceKurmasheva RT, 2006, BRIT J CANCER, V95, P955, DOI 10.1038/sj.bjc.6603353
hcfmusp.relation.referenceLi J, 2014, CELL METAB, V19, P373, DOI 10.1016/j.cmet.2014.01.001
hcfmusp.relation.referenceMcLaughlin-Drubin ME, 2009, VIROLOGY, V384, P335, DOI 10.1016/j.virol.2008.10.006
hcfmusp.relation.referenceMenges CW, 2006, CANCER RES, V66, P5555, DOI 10.1158/0008-5472.CAN-06-0499
hcfmusp.relation.referencePaavonen J, 2007, INT J INFECT DIS, V11, pS3, DOI 10.1016/S1201-9712(07)60015-0
hcfmusp.relation.referencePisani P, 2002, INT J CANCER, V97, P72, DOI 10.1002/ijc.1571
hcfmusp.relation.referenceSCHEFFNER M, 1990, CELL, V63, P1129, DOI 10.1016/0092-8674(90)90409-8
hcfmusp.relation.referenceStelzer MK, 2010, CANCER PREV RES, V3, P1542, DOI 10.1158/1940-6207.CAPR-10-0228
hcfmusp.relation.referenceSun YT, 2008, CELL CYCLE, V7, P3118, DOI 10.4161/cc.7.20.6881
hcfmusp.relation.referenceToschi A, 2009, MOL CELL BIOL, V29, P1411, DOI 10.1128/MCB.00782-08
hcfmusp.relation.referenceWalboomers JMM, 1999, J PATHOL, V189, P12, DOI 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
hcfmusp.relation.referenceWingender E, 2000, NUCLEIC ACIDS RES, V28, P316, DOI 10.1093/nar/28.1.316
hcfmusp.relation.referenceYoon MS, 2015, MOL CELL, V58, P549, DOI 10.1016/j.molcel.2015.03.028
hcfmusp.relation.referenceYoon MS, 2011, J CELL BIOL, V195, P435, DOI 10.1083/jcb.201107033
hcfmusp.relation.referenceZhang LF, 2015, MOL CANCER, V14, DOI 10.1186/s12943-015-0361-x
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