Effect of FBL depletion on cell morphology
This study reveals a previously unrecognized role of FBL in maintaining epithelial characteristics. Its depletion led to a marked reduction in Scribble, a key basolateral protein required for stabilizing E-cadherin at the membrane and sustaining Hippo signaling, thereby preventing TAZ activation. Scribble's bivalent promoter is pre-associated with H3K4me3, H3K27me3, and EZH2. As a nucleolar protein, FBL retains a fraction of EZH2 within the nucleolus, and its loss results in the redistribution of EZH2 into the nucleoplasm, where it engages PRC2-bound promoters, including that of Scribble.Diminished Scribble levels upon FBL knockdown disrupted Hippo signaling, leading to TAZ accumulation and subsequent upregulation of EMT drivers Snail and Foxc2. Additionally, Scribble modulates Akt activity via PHLPP1, and its depletion enhanced Akt-dependent phosphorylation of EZH2, compromising its methyltransferase function. In MCF10A (p53 DN) cells, loss of FBL increased mesenchymal markers (Snail, Twist, Zeb1) while down Overall design: 0.6 million DLD-1 cells were seeded and transfected with siLacZ and siFBL at final concentration of 50nM, in OptiMEM for 6h. Post-transfection cells were incubated at 5% CO2 and 37C for 72h.