PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas.
PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and glioma
Transcription Profiling (Microarray)
A hallmark feature of glioblastoma (GBM) cells is its strong self-renewal potential and immature differentiation state -- stem cell-like properties which may contribute to the plasticity and intense therapeutic resistance of GBM. The molecular basis of the immature differentiation profile remains an area of active investigation. Here, integrated genomic and biological analyses identified PLAGL2 as a potent proto-oncogene targeted for amplification/gain in malignant gliomas as well as in colorectal cancers. High level of PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell (GIC) differentiation while promoting their proliferation and self-renewal capacity under differentiation induction conditions. On the mechanistic level, the PLAGL2 transcriptome analysis revealed that these differentiation suppressive activities are attributable in part to PLAGL2 modulation of Wnt/beta-catenin signaling via up-regulation of Wnt6 ligand as well as Fzd9 and Fzd2 receptor expression. Correspondingly, inhibition of Wnt signaling in PLAGL2-expressing NSC partially restores their differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics on malignant cells.
Study metadata (ISA-Tab: isa_13698_941868.zip)