A Synergistic Anticancer FAK and HDAC Inhibitor Combination Discovered by a Novel Chemical-Genetic High-Content Phenotypic Screen.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
27
03
2019
revised:
22
08
2019
accepted:
22
11
2019
pubmed:
1
12
2019
medline:
12
1
2021
entrez:
1
12
2019
Statut:
ppublish
Résumé
We mutated the focal adhesion kinase (FAK) catalytic domain to inhibit binding of the chaperone Cdc37 and ATP, mimicking the actions of a FAK kinase inhibitor. We reexpressed mutant and wild-type FAK in squamous cell carcinoma (SCC) cells from which endogenous FAK had been deleted, genetically fixing one axis of a FAK inhibitor combination high-content phenotypic screen to discover drugs that may synergize with FAK inhibitors. Histone deacetylase (HDAC) inhibitors represented the major class of compounds that potently induced multiparametric phenotypic changes when FAK was rendered kinase-defective or inhibited pharmacologically in SCC cells. Combined FAK and HDAC inhibitors arrest proliferation and induce apoptosis in a subset of cancer cell lines
Identifiants
pubmed: 31784455
pii: 1535-7163.MCT-19-0330
doi: 10.1158/1535-7163.MCT-19-0330
pmc: PMC7611632
mid: EMS128829
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Focal Adhesion Protein-Tyrosine Kinases
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
637-649Subventions
Organisme : European Research Council
ID : 294440
Pays : International
Organisme : Cancer Research UK
ID : A15703
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C157/A15703
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C157/A24837
Pays : United Kingdom
Informations de copyright
©2019 American Association for Cancer Research.
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