Clear cell renal cell carcinoma (ccRCC) is an aggressive malignancy characterized by
inactivation of the von Hippel-Lindau tumour suppressor gene, the protein product of
which mediates degradation of the transcription factor hypoxia-inducible factor (HIF). GAL3ST1 is a sulfotransferase which catalyzes the production of sulfatide, a plasma membrane sulfolipid previously implicated in metastasis. We observed GAL3ST1
overexpression in primary ccRCC tumours relative to matched-normal tissue and
subsequently asked if GAL3ST1 was a HIF-responsive gene that facilitates ccRCC
metastasis. GAL3ST1 expression was suppressed in ccRCC cells by stable reconstitution of wild-type VHL and also siRNA-mediated knockdown of HIF1alpha and HIF2alpha. Dual luciferase assays and chromatin immunoprecipitation revealed a hypoxia-response element in the GAL3ST1 5’-UTR that appeared to be crucial for HIF-mediated
upregulation. Finally, stable knockdown of GAL3ST1 significantly impeded ccRCC cell
invasion through an in vitro basement membrane mimic. These results suggest GAL3ST1 is a HIF-responsive gene that promotes tumour cell invasion.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33225 |
| Date | 20 November 2012 |
| Creators | Greer, Samantha Nicole |
| Contributors | Ohh, Michael |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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