Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy

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Autor(es): dc.contributorThe Netherlands Cancer Institute-
Autor(es): dc.contributorShanghai Jiao Tong University School of Medicine-
Autor(es): dc.contributorHubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center-
Autor(es): dc.contributorL’Hospitalet del Llobregat-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorL’Hospitalet de Llobre-gat-
Autor(es): dc.contributorParc Cientific de Barcelona (PCB)-
Autor(es): dc.contributorCIBERONC-
Autor(es): dc.contributorInstituto Butantan-
Autor(es): dc.contributorFaculty of Medicine-
Autor(es): dc.contributorEastern Hepatobiliary Surgery Hospital-
Autor(es): dc.contributorInc.-
Autor(es): dc.creatorDias, Matheus Henrique-
Autor(es): dc.creatorFriskes, Anoek-
Autor(es): dc.creatorWang, Siying-
Autor(es): dc.creatorFernandes Neto, Joao M.-
Autor(es): dc.creatorvan Gemert, Frank-
Autor(es): dc.creatorMourragui, Soufiane-
Autor(es): dc.creatorPapagianni, Chrysa-
Autor(es): dc.creatorKuiken, Hendrik J.-
Autor(es): dc.creatorMainardi, Sara-
Autor(es): dc.creatorAlvarez-Villanueva, Daniel-
Autor(es): dc.creatorLieftink, Cor-
Autor(es): dc.creatorMorris, Ben-
Autor(es): dc.creatorDekker, Anna-
Autor(es): dc.creatorvan Dijk, Emma-
Autor(es): dc.creatorWilms, Lieke H. S.-
Autor(es): dc.creatorda Silva, Marcelo S.-
Autor(es): dc.creatorJansen, Robin A.-
Autor(es): dc.creatorMulero-Sánchez, Antonio-
Autor(es): dc.creatorMalzer, Elke-
Autor(es): dc.creatorVidal, August-
Autor(es): dc.creatorSantos, Cristina-
Autor(es): dc.creatorSalazar, Ramón-
Autor(es): dc.creatorWailemann, Rosangela A. M.-
Autor(es): dc.creatorTorres, Thompson E. P.-
Autor(es): dc.creatorDe Conti, Giulia-
Autor(es): dc.creatorRaaijmakers, Jonne A.-
Autor(es): dc.creatorSnaebjornsson, Petur-
Autor(es): dc.creatorYuan, Shengxian-
Autor(es): dc.creatorQin, Wenxin-
Autor(es): dc.creatorKovach, John S.-
Autor(es): dc.creatorArmelin, Hugo A.-
Autor(es): dc.creatorRiele, Hein Te-
Autor(es): dc.creatorvan Oudenaarden, Alexander-
Autor(es): dc.creatorJin, Haojie-
Autor(es): dc.creatorBeijersbergen, Roderick L.-
Autor(es): dc.creatorVillanueva, Alberto-
Autor(es): dc.creatorMedema, Rene H.-
Autor(es): dc.creatorBernards, Rene-
Data de aceite: dc.date.accessioned2025-08-21T21:37:11Z-
Data de disponibilização: dc.date.available2025-08-21T21:37:11Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-07-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1158/2159-8290.CD-23-0216-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/306263-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/306263-
Descrição: dc.descriptionCancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity of such aberrant signaling. Although inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of protein phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor-suppressive resistance.-
Descrição: dc.descriptionEuropean Research Council-
Descrição: dc.descriptionGeneralitat de Catalunya-
Descrição: dc.descriptionNational Natural Science Foundation of China-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionInstituto de Salud Carlos III-
Descrição: dc.descriptionDivision of Molecular Carcinogenesis Oncode Institute The Netherlands Cancer Institute-
Descrição: dc.descriptionDivision of Cell Biology Oncode Institute The Netherlands Cancer Institute-
Descrição: dc.descriptionState Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Renji Hospital Shanghai Jiao Tong University School of Medicine-
Descrição: dc.descriptionDivision of Tumor Biology and Immunology The Netherlands Cancer Institute-
Descrição: dc.descriptionHubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center-
Descrição: dc.descriptionDivision of Molecular Carcinogenesis The Netherlands Cancer Institute-
Descrição: dc.descriptionChemoresistance and Predictive Factors Group Program Against Cancer Therapeutic Resistance (ProCURE) Catalan Institute of Oncology (ICO) Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) L’Hospitalet del Llobregat-
Descrição: dc.descriptionDivision of Molecular Carcinogenesis NKI Robotic and Screening Center The Netherlands Cancer Institute-
Descrição: dc.descriptionDepartment of Biochemistry Institute of Chemistry University of São Paulo, SP-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP), SP-
Descrição: dc.descriptionDepartment of Pathology University Hospital of Bellvitge Bellvitge Biomedical Research Institute (IDIBELL) L’Hospitalet de Llobre-gat-
Descrição: dc.descriptionXenopat S.L. Parc Cientific de Barcelona (PCB)-
Descrição: dc.descriptionDepartment of Medical Oncology Catalan Institute of Oncology (ICO) Oncobell Program Bellvitge Biomedical Research Institute (IDIBELL) CIBERONC-
Descrição: dc.descriptionCenter of Toxins Immune-response and Cell Signaling Instituto Butantan-
Descrição: dc.descriptionDepartment of Clinical and Experimental Oncology Federal University of São Paulo (UNIFESP)-
Descrição: dc.descriptionDepartment of Pathology The Netherlands Cancer Institute-
Descrição: dc.descriptionUniversity of Iceland Faculty of Medicine-
Descrição: dc.descriptionThe Third Department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital-
Descrição: dc.descriptionLixte Biotechnology Holdings Inc.-
Descrição: dc.descriptionDepartment of Chemical and Biological Sciences Institute of Biosciences São Paulo State University (UNESP), SP-
Descrição: dc.descriptionGeneralitat de Catalunya: 2017SGR449-
Descrição: dc.descriptionGeneralitat de Catalunya: 2021 SGR 00184-
Descrição: dc.descriptionNational Natural Science Foundation of China: 22XD1423100-
Descrição: dc.descriptionFAPESP: 82222047-
Descrição: dc.descriptionInstituto de Salud Carlos III: PI19-01320-
Descrição: dc.descriptionInstituto de Salud Carlos III: PI22-00548-
Formato: dc.format1276-1301-
Idioma: dc.languageen-
Relação: dc.relationCancer Discovery-
???dc.source???: dc.sourceScopus-
Título: dc.titleParadoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy-
Tipo de arquivo: dc.typelivro digital-
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