FZD6 (a negative regulator of Wnt signaling) overexpression increased GBM aggressiveness, decreasing PN marker (OLIG2 and SOX2) and increasing MES genes (ALDH1A3 and CD44).[46] Consistently, knockdown and inhibition of Wnt by pharmacological agents confirmed its association with PMT.[46] A similar effect of FZD7 on mesenchymal transformation was also demonstrated in different GBM cell lines.[47] The major signaling pathways associated with MES transition are summarized in Figure 2. The gene discussed is ALDH1A3; the disease is glioblastoma.