The Functional effects of AKR1B10 overexpression in colorectal cancer cell lines

Seza, Esin Gülce
Aldo-keto reductases (AKRs) are nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) dependent oxidoreductases that are involved in many anabolic and catabolic reactions. When they are over-activated, the polyol pathway is activated that results in oxidative stress. AKRs are implicated in many inflammation-associated diseases including diabetes mellitus, asthma, uveitis, sepsis, atherosclerosis, periodontitis, and many cancers. AKR1B10, a member of the AKR family that is also known as small intestine like aldose reductase is highly expressed in the small intestine and colon. Analysis of publicly available microarray datasets indicated that colorectal cancer (CRC) patients showed lower AKR1B10 expression compared to normal tissues, although AKR1B10 was overexpressed in other cancers such as liver cancer. Gene set enrichment analyses indicated significant enrichment of metabolism related genes in tumors that expressed high amounts of AKR1B10. In order to understand the functional effects of AKR1B10, we overexpressed AKR1B10 in CRC cell lines that do not express the protein. We observed no alterations in cellular proliferation or cell cycle; however, cellular motility was reduced, along with a decrease in the nuclear translocation, DNA binding and transcriptional activity of NF-B, which is an important transcription factor that is necessary for cell survival and inflammation. The work carried out in this thesis suggests that the expression of AKR1B10 in colon cancer cells may not directly affect cancer progression by affecting cell proliferation or cell cycle; rather, the protein has a more indirect effect, perhaps through the activation of metabolism related pathways. 


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The Aldo-Keto Reductases (AKR) are nicotinamide adenine dinucleotide (NAD(P)H) dependent oxidoreductases that function in phase 1 metabolismbyreducingaldehydes and ketones into primary and secondary alcohols. Inthis protein superfamily, the expression of AKR1B1 and AKR1B10 enzymes have been linked by us and others to colorectal cancer (CRC). Over-activation of these enzymes in the presence of excess glucose can result in the activation of the polyol pathway, which causes oxidative stress and migh...
Citation Formats
E. G. Seza, “The Functional effects of AKR1B10 overexpression in colorectal cancer cell lines,” M.S. - Master of Science, Middle East Technical University, 2017.