Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity.

Animals Antineoplastic Agents / pharmacology Cell Line, Tumor Enhancer Elements, Genetic Gene Expression Regulation, Neoplastic Humans Integrins / metabolism Lung Neoplasms / genetics Male Mice, Transgenic Prostatic Neoplasms / genetics Retinal Neoplasms / genetics Retinoblastoma / genetics Retinoblastoma Binding Proteins / genetics Small Cell Lung Carcinoma / genetics TEA Domain Transcription Factors / genetics Transcriptional Coactivator with PDZ-Binding Motif Proteins / genetics Ubiquitin-Protein Ligases / genetics Xenograft Model Antitumor Assays YAP-Signaling Proteins / genetics
RB1 TAZ/WWTR1 TEAD YAP cancer plasticity cancer stratification neuroendocrine cancer retinoblastoma retinoma small cell cancers

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
09 08 2021
Historique:
received: 10 06 2020
revised: 17 09 2020
accepted: 24 06 2021
pubmed: 17 7 2021
medline: 8 1 2022
entrez: 16 7 2021
Statut: ppublish

Résumé

Cancer heterogeneity impacts therapeutic response, driving efforts to discover over-arching rules that supersede variability. Here, we define pan-cancer binary classes based on distinct expression of YAP and YAP-responsive adhesion regulators. Combining informatics with in vivo and in vitro gain- and loss-of-function studies across multiple murine and human tumor types, we show that opposite pro- or anti-cancer YAP activity functionally defines binary YAP

Identifiants

DOI: 10.1016/j.ccell.2021.06.016 PMID: 34270926 PMC: PMC8981970
pubmed: 34270926
pii: S1535-6108(21)00338-X
doi: 10.1016/j.ccell.2021.06.016
pmc: PMC8981970
mid: NIHMS1789008
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Integrins 0
RB1 protein, human 0
Retinoblastoma Binding Proteins 0
TEA Domain Transcription Factors 0
Transcriptional Coactivator with PDZ-Binding Motif Proteins 0
WWTR1 protein, human 0
YAP-Signaling Proteins 0
YAP1 protein, human 0
Ubiquitin-Protein Ligases EC 2.3.2.27

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1115-1134.e12

Subventions

Organisme : CIHR
ID : 153128
Pays : Canada
Organisme : NCI NIH HHS
ID : U01 CA253383
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207757
Pays : United States
Organisme : CIHR
ID : FDN 143252
Pays : Canada
Organisme : NCI NIH HHS
ID : R01 CA234162
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000457
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests B.H.L. reports honoraria and non-financial support from AstraZeneca, and has received research funding from Pfizer and AstraZeneca not related to this work.

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Auteurs

Joel D Pearson (JD)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Ophthalmology and Vision Science, University of Toronto, Toronto, ON M5T 3A9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Katherine Huang (K)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Marek Pacal (M)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Sean R McCurdy (SR)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Suying Lu (S)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Arthur Aubry (A)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Ophthalmology and Vision Science, University of Toronto, Toronto, ON M5T 3A9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Tao Yu (T)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Kristine M Wadosky (KM)

Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Letian Zhang (L)

Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Tao Wang (T)

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada.

Alex Gregorieff (A)

Department of Pathology, McGill University and Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, ON H4A 3J1, Canada.

Mohammad Ahmad (M)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada.

Helen Dimaras (H)

Department of Ophthalmology and Vision Science, University of Toronto, Toronto, ON M5T 3A9, Canada; The Department of Ophthalmology & Vision Sciences, Child Health Evaluative Sciences Program, and Center for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Clinical Public Health, Dalla Lana School of Public Health, The University of Toronto, Toronto, ON M5T 3M7, Canada.

Ellen Langille (E)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Susan P C Cole (SPC)

Division of Cancer Biology and Genetics, Queen's University Cancer Research Institute, Kingston, ON K7L 3N6, Canada.

Philippe P Monnier (PP)

Department of Ophthalmology and Vision Science, University of Toronto, Toronto, ON M5T 3A9, Canada; Krembil Research Institute, Vision Division, Krembil Discovery Tower, Toronto, ON M5T 2S8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Benjamin H Lok (BH)

Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Ming-Sound Tsao (MS)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.

Nagako Akeno (N)

Division of Pathology & Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Daniel Schramek (D)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Kathryn A Wikenheiser-Brokamp (KA)

Division of Pathology & Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; The Perinatal Institute Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pathology & Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

Erik S Knudsen (ES)

Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Agnieszka K Witkiewicz (AK)

Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Jeffrey L Wrana (JL)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

David W Goodrich (DW)

Department of Pharmacology & Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Rod Bremner (R)

Lunenfeld Tanenbaum Research Institute, Mt Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Ophthalmology and Vision Science, University of Toronto, Toronto, ON M5T 3A9, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: bremner@lunenfeld.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Éléments activateurs (génétique) › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Intégrines › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Tumeurs de la rétine › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Maladies de l'oeil › Rétinopathies › Tumeurs de la rétine › Rétinoblastome › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines de liaison à la protéine du rétinoblastome › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire à petites cellules › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à domaine TEA › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Transcriptional coactivator with PDZ-binding motif proteins › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Binary pan-cancer classes with distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines de signalisation YAP › Binary pan-cancer classes with distinct...