Tmic-05. fstl1, a marker for peritumoral brain edema and prognosis in glioma

Follistatin-like 1 (FSTL1), encoding a protein similar to follistatin, belongs to the SPARC (the secreted protein, acidic, rich in cysteine) family. In previous studies, FSTL1 was upregulated in glioblastoma and coexpression of FSTL1 with p53 was associated with poor survival of patients with glioblastoma multiformes (GBM). Here we report that, in glioma, FSTL1 promoted cell proliferation, invasion, migration and peritumoral brain edema (PTEB). It not only activated membrane receptor-DIP2A(disco interacting protein 2 homolog A) but also prevented nuclear translocation of DIP2A by competitive binding to DIP2A. A portion of FSTL1 excreted to extracellular space combined to DIP2A and activated AKT signaling. And the other portion of FSTL1 located in cytoplasm interacted with DIP2A to form a functional complex and prevented nuclear translocation of DIP2A. We also detected that DIP2A was involved in the DMAP1(DNA methyltransferase 1 associated protein 1)-HDAC2(histone deacetylase 2) repressive transcription complex through complexation with DMAP1 in nucleus, and then enhanced transcriptional inhibition of FOS(Fos proto-oncogene, AP-1 transcription factor subunit) by the HDAC2 repressive transcription complex. Cytoplasmic FSTL1 acts as a scaffold to impair the interaction between DIP2A and DMAP1-HDAC2 repressive transcription complex, inhibiting the mRNA transcriptional silencing function of HDAC2 on FOS mRNA. We identified the microRNA miR-198, derived from the 3’-...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research