Wnt/β-catenin Signaling Contributes to Tumor Malignancy and Is Targetable in Gastrointestinal Stromal Tumor.

ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. Although the Wnt/β-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed β-catenin and contained active, dephosphorylated nuclear β-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4. Accordingly, in human GIST T1 cells, Wnt stimulation increased β-catenin-mediated transcriptional activity in a reporter assay as well as transcription of the downstream target genes Axin2 and CCND1 In contrast,

SUBMITTER: Zeng S 

PROVIDER: S-EPMC5587376 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature