The Role of Hypoxia on PORCN and WLS Expression in Human Embryonic Kidney (HEK293T) and Human Colon Cancer (HCT-116T) Cells

WNT proteins activate different intracellular signal transduction pathways, regulate cell proliferation, adult tissue homeostasis and the progression of disease. In this thesis, I examine the WNT modifying proteins: Porcupine (PORCN) and GPR177/Wntless (WLS). PORCN is responsible for palmitoylation of WNT proteins, while WLS has been suggested to be responsible for their glycosylation. Given that tumor microenvironments in the body are low in oxygen (hypoxic), I hypothesized that PORCN and WLS are regulated by the Hypoxia-Inducible Factor (HIF) transcription factors. We used RNA interference to knockdown HIF-1 alpha expression in HCT116 cells to determine how loss of HIF-1 alpha affected PORCN, WLS and WNT3A expression. We provide the first evidence that PORCN, WLS and WNT3A may be directly regulated by HIF-1 alpha in response to hypoxia. PORCN and WLS proteins may also impact WNT3A post-transcriptional modifications under these conditions.