In GBM tissues PIAS3 is downregulated, and the SMAD6-induced ubiquitination-mediated degradation of PIAS3 induces STAT3-mediated proliferation and stem-like cell initiation [188], while inhibition of PIAS3 by TRIM8 by a similar mechanism maintains STAT3-mediated stemness and self-renewal in GBM stem-like cells [189]. Here, SMAD6 is linked to glioblastoma.