PUBLICATION

Systematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor

Authors
Daakour, S., Hajingabo, L.J., Kerselidou, D., Devresse, A., Kettmann, R., Simonis, N., Dequiedt, F., Twizere, J.C.
ID
ZDB-PUB-171003-11
Date
2016
Source
BMC cancer   16: 335 (Journal)
Registered Authors
Keywords
Acute lymphoblastic leukemia, Cancer genes, EXT1, Interactome, Notch pathway
MeSH Terms
  • Animals
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mutation
  • N-Acetylglucosaminyltransferases/metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*
  • Protein Interaction Mapping
  • Receptor, Notch1/metabolism*
  • Signal Transduction
  • Transcription, Genetic
  • Zebrafish
PubMed
27229929 Full text @ BMC Cancer
Abstract
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.
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.
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.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping