Article (Scientific journals)
Systematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor.
Daakour, Sarah; Hajingabo, Leon Juvenal; Kerselidou, Despoina et al.
2016In BMC Cancer, 16 (1), p. 335
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Keywords :
Acute lymphoblastic leukemia; Cancer genes; EXT1; Interactome; Notch pathway
Abstract :
[en] BACKGROUND: Perturbed genotypes in cancer can now be identified by whole genome sequencing of large number of diverse tumor samples, and observed gene mutations can be used for prognosis and classification of cancer subtypes. Although mutations in a few causative genes are directly linked to key signaling pathways perturbation, a global understanding of how known cancer genes drive oncogenesis in human is difficult to assess. METHODS: We collected available information about mutated genes in Acute Lymphoblastic Leukemia (ALL). Validated human protein interactions (PPI) were collected from IntAct, HPRD and BioGRID interactomics databases, or obtained using yeast two-hybrid screening assay. RESULTS: We have mapped interconnections between 116 cancer census gene products associated with ALL. Combining protein-protein interactions data and cancer-specific gene mutations information, we observed that 63 ALL-gene products are interconnected and identified 37 human proteins interacting with at least 2 ALL-gene products. We highlighted exclusive and coexistence genetic alterations in key signaling pathways including the PI3K/AKT and the NOTCH pathways. We then used different cell lines and reporter assay systems to validate the involvement of EXT1 in the Notch pathway. CONCLUSION: We propose that novel ALL-gene candidates can be identified based on their functional association with well-known cancer genes. We identified EXT1, a gene not previously linked to ALL via mutations, as a common interactor of NOTCH1 and FBXW7 regulating the NOTCH pathway in an FBXW7-dependend manner.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Daakour, Sarah ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Hajingabo, Leon Juvenal
Kerselidou, Despoina 
Devresse, Aurelie
Kettmann, Richard ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Simonis, Nicolas
Dequiedt, Franck  ;  Université de Liège > GIGA-Research
Twizere, Jean-Claude  ;  Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Language :
English
Title :
Systematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor.
Publication date :
2016
Journal title :
BMC Cancer
eISSN :
1471-2407
Publisher :
BioMed Central, London, United Kingdom
Volume :
16
Issue :
1
Pages :
335
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 June 2016

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