Importantly, our study reveals an increased abundance and activity of nucleophosmin (NPM1) that could be linked with initiation of centrosome amplification and mitosis as a novel molecular trait of BRAFV600E-mutated colon cancer in vitro, in silico and in tumor tissues from colon adenocarcinoma patients and provides evidence to demonstrate the roles of NPM1 and its interaction partner c-Myc in conveying the resistance to BRAF inhibitor vemurafenib. Here, MYC is linked to colon adenocarcinoma.