SOX2 and neoplasm: By inactivating FBXW2 E3, MLN4924 causes accumulation of MSX2 to transcriptionally repress SOX2 expression.52,263 Biologically, MLN4924, via depleting SOX2, overcomes tamoxifen resistance of breast cancer cells, as demonstrated by both in vitro proliferation and survival assays, and in vivo xenograft tumor model52 (Fig. 7).