ArticleBritish journal of cancer2017
RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.Molecular oncology · 2024Article
- Uncovering hidden cancer self-dependencies through analysis of shRNA-level dependency scores.Scientific reports · 2024Article
- FBXW7 in breast cancer: mechanism of action and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2023Review
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas.Molecular oncology · 2021Article
- Review
- TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis.British journal of cancer · 2019Article
- SGC-GAK-1: A Chemical Probe for Cyclin G Associated Kinase (GAK).Journal of medicinal chemistry · 2019Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundF-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in multiple cancers through genetic deletion and mutations in a broad range of tumours. Loss of FBXW7 functionality results in the stabilisation of multiple major oncoproteins, culminating in increased cellular proliferation and pro-survival pathways, cell cycle deregulation, chromosomal instability and altered metabolism. Currently, there is no therapy to specifically target FBXW7-deficient tumours.
methodsWe performed a siRNA kinome screen to identify synthetically lethal hits to FBXW7 deficiency.
resultsWe identified and validated cyclin G-associated kinase (GAK) as a potential new therapeutic target. Combined loss of FBXW7 and GAK caused cell cycle defects, formation of multipolar mitoses and the induction of apoptosis. The synthetic lethal mechanism appears to be independent of clathrin-mediated receptor endocytosis function of GAK.
conclusionsThese data suggest a putative therapeutic strategy for a large number of different types of human cancers with FBXW7 loss, many of which have a paucity of molecular abnormalities and treatment options.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.