Evaluation of functional changes in akr1b1 and akr1b10 overexpressing colorectal cancer cell lines

Güderer, İsmail
Aldo-keto reductases (AKRs) are nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzymes with diverse cellular metabolism functions. AKR1B1 and AKR1B10 are two of the most studied enzymes in the AKR family. AKR1B1 reduces excess glucose into sorbitol using reducing electrons from NADPH, and the hyperactivation of the AKR1B1 pathways is associated with oxidative stress and cell death. AKR1B10 is a poor reductant of glucose but is a vital enzyme that can metabolize retinol and many other drugs and therefore is implicated in cancer development. Our previous research has shown that high expression of AKR1B1 and AKR1B10 in colorectal cancer can have divergent effects. Thus, while high expression of AKR1B1 was associated with a strong epithelial to mesenchymal (EMT) and pro-inflammatory phenotype, high expression of AKR1B10 showed activation of nutrient-sensing pathways. In order to better understand the functional effects and underlying cellular signaling pathways, we overexpressed both enzymes in cell lines RKO and SW480 that do not endogenously express AKR1B1 or AKR1B10. Functional assays showed no significant alterations in cellular proliferation in 2D cell culture, which was also reflected in no alterations in colony formation capacity. AKR1B10 overexpressing cells had a greater vulnerability to serum starvation reflected by a high number of cells arrested in the G1 phase of the cell cycle. AKR1B1 overexpressing cells compared to AKR1B10 overexpressing cells showed significantly higher motility, confirming our previous data. RNA sequencing of AKR1B1 and AKR1B10 overexpressing RKO cells indicated that gene ontology (GO) terms previously established in high AKR1B1 or AKR1B10 expressing tumor samples (that have an expression from both epithelial and stromal compartments) overlapped with the GO terms obtained in RKO cells. Thus, high AKR1B1 overexpressing cells were significantly associated with ROS-related processes, whereas AKR1B10 overexpressing cells were significantly associated with the inhibition of metabolic and biosynthetic processes.


Evaluation of an aldo-keto reductase gene signature with prognostic significance in colon cancer via activation of epithelial to mesenchymal transition and the p70S6K pathway
Canli, Secil Demirkol; Seza, Esin Gulce; Sheraj, Ilir; Gomceli, Ismail; Turhan, Nesrin; Carberry, Steven; Prehn, Jochen H. M.; GÜRE, ALİ OSMAY; Banerjee, Sreeparna (Oxford University Press (OUP), 2020-09-01)
AKR1B1 and AKR1B10, members of the aldo-keto reductase family of enzymes that participate in the polyol pathway of aldehyde metabolism, are aberrantly expressed in colon cancer. We previously showed that high expression of AKR1B1 (AKR1B1(HIGH)) was associated with enhanced motility, inflammation and poor clinical outcome in colon cancer patients. Using publicly available datasets and ex vivo gene expression analysis (n = 51, Ankara cohort), we have validated our previous in silico finding that AKR1B1(HIGH) ...
Evaluation of functional changes in akr overexpressing colorectal cell line sw480
Ermiş, Çağdaş; Banerjee, Sreeparna; Erel Göktepe, İrem; Department of Biochemistry (2021-2-02)
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...
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Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cell-cell and cell-microenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line that can undergo spontaneous differentiation when grown past confluency, we observed a loss of VCAM1 (vascular cell adhesion molecule-1) expression while ICAM1 (intercellular cell adhesion molecule-1...
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Tranilast is an antiallergic drug that interferes with proliferation and migration of vascular smooth muscle cell induced by platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1). We investigated the local effect of tranilast on neointimal hyperplasia using tranilastcoated prosthetic grafts. The inner sides of the thin-walled polytetrafluoroethylene (PTFE) grafts were coated with chitosan and tranilast containing chitosan solution. Wistar albino rats (32) were used in the ...
Effects of the quercetin derivative CHNQ, a potent aldo- keto reductase inhibitor, on akr1b1 silenced HCT-116 colorectal cancer cells
Taşkoparan, Betül; Banerjee, Sreeparna; Department of Biology (2016)
Aldo-keto reductases (AKRs) are NAD(P)H dependent oxidoreductases that are known to be involved in the biosynthesis, metabolism and detoxification of a number of substrates including glucose. These enzymes are therefore implicated in the development of diabetic complications. Additionally, this family of enzymes, particularly AKR1B1, has been shown to be involved in pathology of inflammation- associated diseases such as atherosclerosis, asthma, uveitis, sepsis, arthritis, periodontitis and cancer, including...
Citation Formats
İ. Güderer, “Evaluation of functional changes in akr1b1 and akr1b10 overexpressing colorectal cancer cell lines,” M.S. - Master of Science, Middle East Technical University, 2021.