One study performed with cell lines, human tissues and mouse models showed that upregulation of the co-activator CRTC1 stimulates expression of the COX-2 gene and the production of prostaglandin PGE2, which in turn leads to dephosphorylation and activation of CRTC1, closing the feedback loop that increases tumorigenicity of colorectal cancer [65]. Here, CRTC1 is linked to colorectal cancer.