CDK5 and colorectal cancer: Furthermore, Cdk5 can amplify pro-invasive programs by activating downstream signaling cascades; in colorectal cancer, it directly phosphorylates ERK5 at Thr732 within its C-terminal transcriptional activation domain, a key step that enables ERK5-dependent activating protein 1 (AP-1) coactivation and subsequent upregulation of oncogenic targets including c-Myc, VEGFA, and MMP1 [108].