11β-Prostaglandin F2α, a bioactive metabolite catalyzed by AKR1C3, stimulates prostaglandin F receptor and induces slug expression in breast cancer

Yoda, Takashi; Kikuchi, Keiko; Miki, Yasuhiro; Onodera, Yoshiaki; Hata, Shuko; Takagi, Kiyoshi; Nakamura, Yasuhiro; Higuchi, Hisashi; Ishida, Toru; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu; McNamara, Keely May

doi:10.1016/j.mce.2015.07.008

Cited by 23 publications

(17 citation statements)

References 70 publications

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“…AKR1C3 is responsible for the reduction of PGD2 to11β-PGF2α, both of which were reported to demonstrate similar affinities toward their cognate receptor, Prostaglandin receptor (FP receptor). And the action of FP receptor ligands results in carcinoma cell survival in breast cancer (Yoda et al, 2015). AKR1C3 is also associated with doxorubicin resistance in human breast cancer (Zhong et al, 2015).…”

Section: Catalytic-dependent Biological Role and Cancermentioning

confidence: 99%

Aldo–Keto Reductase AKR1C1–AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy

et al. 2017

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Aldo–keto reductases comprise of AKR1C1–AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. Recent studies have provided evidences of strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Mechanistically, most studies focus on the catalytic-dependent function of AKR1C isoforms, like their impeccable roles in prostate cancer, breast cancer, and drug resistance due to the broad substrates specificity. However, accumulating clues showed that catalytic-independent functions also played critical roles in regulating biological events. This review summarizes the catalytic-dependent and -independent roles of AKR1Cs, as well as the small molecule inhibitors targeting these family members.

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Section: Catalytic-dependent Biological Role and Cancermentioning

confidence: 99%

Aldo–Keto Reductase AKR1C1–AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy

et al. 2017

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“…Although advances in combination chemotherapy and/or radiotherapy have prolonged the overall survival of EAC patients, the high rate of resistance to conventional chemotherapy is still the main obstacle to the effective therapy of EAC [ 37 , 38 ]. AKR1C3, as a key member of the AKR1Cs subfamily, has been identified as a potential novel therapeutic target in multiple types of cancer [ 13 , 39 , 40 ]. Recently, AKR1C3 has been reported to be upregulated in many human tumors and identified as a prognostic marker in various cancers, including breast cancer, prostate cancer and colon cancer [ 14 , 15 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Aldo-Keto Reductase 1C3 Mediates Chemotherapy Resistance in Esophageal Adenocarcinoma via ROS Detoxification

Zhou

Wang

et al. 2021

Cancers

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Esophageal adenocarcinoma (EAC) is one of the most lethal malignancies, and limits promising treatments. AKR1C3 represents a therapeutic target to combat the resistance in many cancers. However, the molecular mechanism of AKR1C3 in the chemotherapy resistance of EAC is still unclear. We found that the mRNA level of AKR1C3 was higher in EAC tumor tissues, and that high AKR1C3 expression might be associated with poor overall survival of EAC patients. AKR1C3 overexpression decreased cell death induced by chemotherapeutics, while knockdown of AKR1C3 attenuated the effect. Furthermore, we found AKR1C3 was inversely correlated with ROS production. Antioxidant NAC rescued chemotherapy-induced apoptosis in AKR1C3 knockdown cells, while the GSH biosynthesis inhibitor BSO reversed a protective effect of AKR1C3 against chemotherapy. AKT phosphorylation was regulated by AKR1C3 and might be responsible for eliminating over-produced ROS in EAC cells. Intracellular GSH levels were modulated by AKR1C3 and the inhibition of AKT could reduce GSH level in EAC cells. Here, we reported for the first time that AKR1C3 renders chemotherapy resistance through controlling ROS levels via AKT signaling in EAC cells. Targeting AKR1C3 may represent a novel strategy to sensitize EAC cells to conventional chemotherapy.

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“…In contrast, the inhibition of endogenous PGE through the genetic deletion of prostaglandin E synthase (PTGES) has been shown to suppress intestinal tumorigenesis in mouse models [ 40 ]. Similarly, PGF2-α, which is a metabolite of PGE2 has also been reported to be increased in several types of carcinoma [ 41 – 43 ]. As shown in a previously published study on non-small cell lung cancer (NSCLC) increased concentrations of TXB2 were also found in mice [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Measurement of Serum and Hepatic Eicosanoids by Liquid Chromatography Tandem-Mass Spectrometry (LC-MS/MS) in a Mouse Model of Hepatocellular Carcinoma (HCC) with Delivery of c-Met and Activated β-Catenin by Hepatocyte Hydrodynamic Injection

Lin

et al. 2018

Med Sci Monit

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BackgroundMost forms of cancer, including hepatocellular carcinoma (HCC), are associated with varying degrees of chronic inflammation. The association between the expression of eicosanoids, which are bioactive lipid mediators of inflammation, and HCC remains unknown. The aim of this study was to measure serum and hepatic eicosanoids in a mouse model of HCC with the delivery of c-Met and activated β-catenin by hepatocyte hydrodynamic injection.Material/MethodsThe HCC mouse model, and normal control mice, were used in this study with co-delivery of human c-Met combined with activated β-catenin into hepatocytes through hydrodynamic injection. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis was used to measure serum and hepatic eicosanoid levels.ResultsThe combined activation of c-Met and β-catenin was induced in the HCC mouse model. LC-MS/MS showed that a total of 13 eicosanoids in serum and 12 eicosanoids in liver tissue were significantly increased in the HCC mice, when compared with control mice.ConclusionsIn a mouse model of HCC, co-activation of the c-Met and β-catenin signaling pathway resulted in increased levels of serum and hepatic eicosanoids.

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11β-Prostaglandin F2α, a bioactive metabolite catalyzed by AKR1C3, stimulates prostaglandin F receptor and induces slug expression in breast cancer

Cited by 23 publications

References 70 publications

Aldo–Keto Reductase AKR1C1–AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy

Aldo–Keto Reductase AKR1C1–AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy

Aldo-Keto Reductase 1C3 Mediates Chemotherapy Resistance in Esophageal Adenocarcinoma via ROS Detoxification

Measurement of Serum and Hepatic Eicosanoids by Liquid Chromatography Tandem-Mass Spectrometry (LC-MS/MS) in a Mouse Model of Hepatocellular Carcinoma (HCC) with Delivery of c-Met and Activated β-Catenin by Hepatocyte Hydrodynamic Injection

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