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

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Supplemental Files: 

Creator: 

Clinch, Matthew Edgar

Date: 

2022

Abstract: 

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.

Subject: 

Cell biology
Biology - Molecular
Genetics

Language: 

English

Publisher: 

Carleton University

Contributor: 

Author: 
Matthew E. Clinch

Thesis Degree Name: 

Master of Science: 
M.Sc.

Thesis Degree Level: 

Master's

Thesis Degree Discipline: 

Biology

Parent Collection: 

Theses and Dissertations

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