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Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway.
Kurppa, Kari J; Liu, Yao; To, Ciric; Zhang, Tinghu; Fan, Mengyang; Vajdi, Amir; Knelson, Erik H; Xie, Yingtian; Lim, Klothilda; Cejas, Paloma; Portell, Andrew; Lizotte, Patrick H; Ficarro, Scott B; Li, Shuai; Chen, Ting; Haikala, Heidi M; Wang, Haiyun; Bahcall, Magda; Gao, Yang; Shalhout, Sophia; Boettcher, Steffen; Shin, Bo Hee; Thai, Tran; Wilkens, Margaret K; Tillgren, Michelle L; Mushajiang, Mierzhati; Xu, Man; Choi, Jihyun; Bertram, Arrien A; Ebert, Benjamin L; Beroukhim, Rameen; Bandopadhayay, Pratiti; Awad, Mark M; Gokhale, Prafulla C; Kirschmeier, Paul T; Marto, Jarrod A; Camargo, Fernando D; Haq, Rizwan; Paweletz, Cloud P; Wong, Kwok-Kin; Barbie, David A; Long, Henry W; Gray, Nathanael S; Jänne, Pasi A.
Afiliação
  • Kurppa KJ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Liu Y; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
  • To C; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Zhang T; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
  • Fan M; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
  • Vajdi A; Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Knelson EH; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Xie Y; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Lim K; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Cejas P; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Portell A; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Lizotte PH; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Ficarro SB; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Dep
  • Li S; Division of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
  • Chen T; Division of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
  • Haikala HM; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Wang H; School of Life Science and Technology, Tongji University, 200092 Shanghai, China.
  • Bahcall M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Gao Y; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02215, USA.
  • Shalhout S; Stem Cell Program, Boston Children's Hospital, Boston, MA 02215, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Boettcher S; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Shin BH; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Thai T; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Wilkens MK; Experimental Therapeutics Core, Dana-Farber Cancer Institute, Boston, MA 02210, USA.
  • Tillgren ML; Experimental Therapeutics Core, Dana-Farber Cancer Institute, Boston, MA 02210, USA.
  • Mushajiang M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Xu M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Choi J; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Bertram AA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Ebert BL; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Beroukhim R; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Bandopadhayay P; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02115, USA.
  • Awad MM; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Gokhale PC; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Experimental Therapeutics Core, Dana-Farber Cancer Institute, Boston, MA 02210, USA.
  • Kirschmeier PT; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Marto JA; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Dep
  • Camargo FD; Stem Cell Program, Boston Children's Hospital, Boston, MA 02215, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
  • Haq R; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Paweletz CP; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Wong KK; Division of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
  • Barbie DA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Long HW; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Gray NS; Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
  • Jänne PA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, LC4114
Cancer Cell ; 37(1): 104-122.e12, 2020 01 13.
Article em En | MEDLINE | ID: mdl-31935369
ABSTRACT
Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Regulação Neoplásica da Expressão Gênica / Apoptose / Resistencia a Medicamentos Antineoplásicos / Proteínas Adaptadoras de Transdução de Sinal / Neoplasias Pulmonares Limite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Regulação Neoplásica da Expressão Gênica / Apoptose / Resistencia a Medicamentos Antineoplásicos / Proteínas Adaptadoras de Transdução de Sinal / Neoplasias Pulmonares Limite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos