Reference Detail

Ref Type Journal Article
PMID (20028853)
Authors Baryawno N, Sveinbjornsson B, Eksborg S, Chen CS, Kogner P, Johnsen JI
Title Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth.
Journal Cancer research
Vol 70
Issue 1
Date 2010 Jan 1
URL
Abstract Text Activation of the beta-catenin and receptor kinase pathways occurs often in medulloblastoma, the most common pediatric malignant brain tumor. In this study, we show that molecular cross-talk between the beta-catenin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways is crucial to sustain medulloblastoma pathophysiology. Constitutive activation of phosphoinositide-dependent protein kinase 1 (PDK1), Akt, and phosphorylation of [corrected] glycogen synthase kinase 3beta (GSK-3beta) was detected by immunohistochemistry in all primary medulloblastomas examined (n = 41). Small-molecule inhibitors targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc. The PDK1 inhibitor OSU03012 induced mitochondrial-dependent apoptosis of medulloblastoma cells and enhanced the cytotoxic effects of chemotherapeutic drugs in a synergistic or additive manner. In vivo, OSU03012 inhibited the growth of established medulloblastoma xenograft tumors in a dose-dependent manner and augmented the antitumor effects of mammalian target of rapamycin inhibitor CCI-779. These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt signaling pathway as a therapeutic target in treatment of this disease.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
CTNNB1 T41I PDPK1 Inhibitor
CTNNB1 G34A PDPK1 Inhibitor
CTNNB1 S37T PDPK1 Inhibitor
CTNNB1 S45A PDPK1 Inhibitor
CTNNB1 N387K PDPK1 Inhibitor
CTNNB1 G34V PDPK1 Inhibitor
CTNNB1 P44A PDPK1 Inhibitor
CTNNB1 S37A PDPK1 Inhibitor
CTNNB1 A39T PDPK1 Inhibitor
CTNNB1 S33Y PDPK1 Inhibitor
CTNNB1 S33C PDPK1 Inhibitor
CTNNB1 S45del PDPK1 Inhibitor
CTNNB1 E67K PDPK1 Inhibitor
CTNNB1 S33L PDPK1 Inhibitor
CTNNB1 S45Y PDPK1 Inhibitor
CTNNB1 S45T PDPK1 Inhibitor
CTNNB1 W25_D32del PDPK1 Inhibitor
CTNNB1 A21T PDPK1 Inhibitor
CTNNB1 T41A PDPK1 Inhibitor
CTNNB1 S37Y PDPK1 Inhibitor
CTNNB1 P44_S45del PDPK1 Inhibitor
CTNNB1 D32E PDPK1 Inhibitor
CTNNB1 S33F PDPK1 Inhibitor
CTNNB1 G34E PDPK1 Inhibitor
CTNNB1 D32Y PDPK1 Inhibitor
CTNNB1 A43T PDPK1 Inhibitor
CTNNB1 H36Y PDPK1 Inhibitor
CTNNB1 S37C PDPK1 Inhibitor
CTNNB1 S33N PDPK1 Inhibitor
CTNNB1 I35S PDPK1 Inhibitor
CTNNB1 D32G PDPK1 Inhibitor
CTNNB1 D32N PDPK1 Inhibitor
CTNNB1 D32A PDPK1 Inhibitor
CTNNB1 S33T PDPK1 Inhibitor
CTNNB1 H36P PDPK1 Inhibitor
CTNNB1 A13T PDPK1 Inhibitor
CTNNB1 A39G PDPK1 Inhibitor
CTNNB1 W383R PDPK1 Inhibitor
CTNNB1 S33P PDPK1 Inhibitor
CTNNB1 K335I PDPK1 Inhibitor
CTNNB1 A43P PDPK1 Inhibitor
CTNNB1 G48D PDPK1 Inhibitor
CTNNB1 S45N PDPK1 Inhibitor
CTNNB1 S37F PDPK1 Inhibitor
CTNNB1 G38P PDPK1 Inhibitor
CTNNB1 S37P PDPK1 Inhibitor
CTNNB1 E54K PDPK1 Inhibitor
CTNNB1 G34R PDPK1 Inhibitor
CTNNB1 S45F PDPK1 Inhibitor
CTNNB1 I35T PDPK1 Inhibitor
CTNNB1 D32H PDPK1 Inhibitor
CTNNB1 S45C PDPK1 Inhibitor
CTNNB1 S33A PDPK1 Inhibitor
CTNNB1 I35N PDPK1 Inhibitor
CTNNB1 V22A PDPK1 Inhibitor
CTNNB1 S45P PDPK1 Inhibitor
CTNNB1 act mut PDPK1 Inhibitor
CTNNB1 D32V PDPK1 Inhibitor
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
OSU03012 OSU03012 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
OSU03012 AR-12|OSU-03012 PDPK1 Inhibitor 10 OSU03012 is an inhibitor of PDPK1, which can indirectly inhibit beta-catenin by blocking Akt signaling resulting in apoptosis and anti-tumor activity (PMID: 20028853).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References