This paper examines the response of the WNT signaling pathway involved in the development of colorectal cancer. WNT signaling controls the development and “stemness” of cells and the deregulation of this pathway has been shown to result in various types of cancers. Porcupine (PORCN) is a palmitoyltransferase and Wntless (WLS) is a dedicated WNT transport protein involved in WNT signaling. This study examines the response of this pathway to stresses found in the tumour microenvironment, including hypoxia, oxidative stress and endoplasmic reticulum stress.