The transcription factor forkhead, transcription factor O subfamily 3a (FoxO3a) plays a role in the regulation of BIM expression and is associated to the pathogenesis of colorectal cancer.
BH3-mimetic compounds recapitulated the effect of Bim not only in the adenomas but also in human CRC organoids that had lost responsiveness to TGF-β-induced apoptosis.
BIM is de-phosphorylated and upregulated following MEK1/2 inhibition in all CRC cell lines studied and knockdown of BIM reduces cell death, indicating that repression of BIM is a major part of the ability of BRAF(V600E) to confer growth factor-independent survival.