Gene interactions and pathways from curated databases and text-mining
Br J Cancer 2006, PMID: 16404421

mTOR signaling: implications for cancer and anticancer therapy.

Petroulakis, E; Mamane, Y; Le Bacquer, O; Shahbazian, D; Sonenberg, N

Mounting evidence links deregulated protein synthesis to tumorigenesis via the translation initiation factor complex eIF4F. Components of this complex are often overexpressed in a large number of cancers and promote malignant transformation in experimental systems. mTOR affects the activity of the eIF4F complex by phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins. The immunosuppressant rapamycin specifically inhibits mTOR activity and retards cancer growth. Importantly, mutations in upstream negative regulators of mTOR cause hamartomas, haemangiomas, and cancers that are sensitive to rapamycin treatment. Such mutations lead to increased eIF4F formation and consequently to enhanced translation initiation and cell growth. Thus, inhibition of translation initiation through targeting the mTOR-signalling pathway is emerging as a promising therapeutic option.

Diseases/Pathways annotated by Medline MESH: Cell Transformation, Neoplastic, Neoplasms
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Text Mining Data

eIF4F — mTOR: " mTOR affects the activity of the eIF4F complex by phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: Complex of TSC1-TSC2 → AKT1 (decreases, AKT1 Activity, TSC1/TSC2 Activity)
    Evidence: In turn, Akt phosphorylates the tuberous scleorisis complex, TSC1/TSC2 (hamartin/tuberin) that serves as a GTPase activating protein (GAP) for the small G protein, Ras homolog enriched in brain (Rheb).
  • OpenBEL Selventa BEL large corpus: IRS1 → IRS1 (directlyDecreases, IRS1 Activity)
    Evidence: S6K was shown to directly phosphorylate IRS-1 to inhibit phosphatidylinositol-3-kinase (PI3K) and Akt activation (Harrington ete al, 2004).
  • OpenBEL Selventa BEL large corpus: None → PTEN (increases, Activity)
    Evidence: PTEN is a lipid phosphatase that acts on the lipid substsrate PIP3 to convert it to PIP2.
  • OpenBEL Selventa BEL large corpus: EIF4B → RPS6KB1 (directlyIncreases, EIF4B Activity)
    Evidence: The translation factor eIF4B, which stimulates the activity of eIF4A in unwinding dublex RNA, is phosphorylated by S6K1 on serine 422 (Raugh et al, 2004).
  • OpenBEL Selventa BEL large corpus: IRS1 → RPS6KB1 (decreases, RPS6KB1 Activity, IRS1 Activity)
    Evidence: S6K was shown to directly phosphorylate IRS-1 to inhibit phosphatidylinositol-3-kinase (PI3K) and Akt activation (Harrington ete al, 2004).
  • OpenBEL Selventa BEL large corpus: IRS1 → RPS6KB1 (increases, IRS1 Activity)
    Evidence: S6K was shown to directly phosphorylate IRS-1 to inhibit phosphatidylinositol-3-kinase (PI3K) and Akt activation (Harrington ete al, 2004).