Year: 2016
Type: dissertation
Abstract: Tumor hypoxia is the situation where tumor cells have been deprived of oxygen.In order to support continuous growth and proliferation in hypoxic condition, cancer cells are found to alter their metabolism by modulating expression of many relevant genes.Investigation of the metabolic reprogramming and underlying mechanism of cancer cells under hypoxic condition is critical in our understanding of cancer cell physiology and development of anti-cancer therapeutics.Unexpectedly, I found that FBI-1, initially characterized as proto-oncogene, represses MCT4 gene transcription under both normoxic and more potently, under hypoxic conditions by binding to the FRE (FBI-1 responsive element) of the promoter.FBI-1 also binds to the HRE (HIF-1α responsive element) of the MCT4 promoter and inhibits HIF-1α binding. FBI-1 enhances HIF-1α protein degradation.Interestingly, FBI-1 expression can be negatively regulated at transcription level by RelA/p65 binding to the FBI-1 promoter under hypoxic condition, which increases MCT4 expression.Considering that NF-kB is activated in the cells under hypoxic condition, repression of FBI-1 expression might facilitate cancer cell growth by exporting glycolysis derived lactate through induction of MCT4.Overall, in hypoxic cancer cells, FBI-1 is repressed to induce MCT4-mediated efflux of lactate and H + , which makes extracellular pH acidic and support cancer cell proliferation.
Author: 김민영
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3208316554