Fig. 8.

Schematic representation of the proposed mechanism of BMP6 signaling pathway regulated by PSMD14-ALK2 axis in colorectal cancers. ALK2 type I receptor is polyubiquitinated by E3 ligase Smurf1 and subsequently degraded in the absence of BMP6. Upon treatment of BMP6, PSMD14 binds to ALK2 protein and deubiquitinates the K48-linked polyubiquitin chains of ALK2 protein, resulting in the increase of ALK2 stability and thus leads to the initiation of BMP6 signaling pathway. This initiation of BMP6 signaling pathway facilitates tumor growth, cancer stemness and chemoresistance in colorectal cancers.