Role of aldo‐keto reductase family 1 member B1 (AKR1B1) in the cancer process and its therapeutic potential

Abstract

The role of aldo‐keto reductase family 1 member B1 (AKR1B1) in cancer is not totally clear but growing evidence is suggesting to have a great impact on cancer progression. AKR1B1 could participate in a complicated network of signalling pathways, proteins and miRNAs such as mir‐21 mediating mechanisms like inflammatory responses, cell cycle, epithelial to mesenchymal transition, cell survival and apoptosis. AKR1B1 has been shown to be mostly overexpressed in cancer. This overexpression has been associated with inflammatory mediators including nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NFκB), cell cycle mediators such as cyclins and cyclin‐dependent kinases (CDKs), survival proteins and pathways like mammalian target of rapamycin (mTOR) and protein kinase B (PKB) or AKT, and other regulatory factors in response to reactive oxygen species (ROS) and prostaglandin synthesis. In addition, inhibition of AKR1B1 has been shown to mostly have anti‐cancer effects. Several studies have also suggested that AKR1B1 inhibition as an adjuvant therapy could render tumour cells more sensitive to anti‐cancer therapy or alleviate the adverse effects of therapy. AKR1B1 could also be considered as a potential cancer diagnostic biomarker since its promoter has shown high levels of methylation. Although pre‐clinical investigations on the role of AKR1B1 in cancer and the application of its inhibitors have shown promising results, the lack of clinical studies on AKR1B1 inhibitors has hampered the use of these drugs to treat cancer. Thus, there is a need to conduct more clinical studies on the application of AKR1B1 inhibitors as adjuvant therapy on different cancers.

Proteomic Characterization of Two Extracellular Vesicle Subtypes Isolated from Human Glioblastoma Stem Cell Secretome by Sequential Centrifugal Ultrafiltration

“…Finally, ATP synthase subunit beta together with the subunit alpha forms one of the two structural domains of ATPase, which is linked to mitochondrial membrane and produces ATP from ADP in the presence of a proton gradient across the membrane generated by electron transport complexes of the respiratory chain [ 53 ]. As for MV top proteins, those selected in Exos have also mostly been detected in different tumors, likely playing a role in cancer progress [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ].…”

Identification of a Novel Lipid Metabolism-Related Gene Signature in Prognosis of Bladder Cancer

“…Aldo-keto reductase 1 member B1 (AKR1B1) could be involved in various signaling pathways, such as epithelial to mesenchymal transition (EMT) [30], in ammatory responses [31], and mTOR pathway [32]. Growing study suggested that AKR1B was involved in cancer progression [33]. Carnitine palmitoyltransferase 1B (CPT1B) has been reported to be related with tumor proliferation and metastasis through regulating EMT in BLCA [34].…”

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

“…AKR1B1, a member of the aldo/keto reductase superfamily, was associated with the poor survival outcomes of basal-like breast cancer and can promote the occurrence and metastasis of cancer by activating epithelial-mesenchymal transition [26]. AKR1B1 was highly expressed in multiple tumors and was associated with nuclear factor kappalight-chain-enhancer of activated B cells (NFκB), survival proteins and pathways like the mammalian target of rapamycin (mTOR) and protein kinase B (PKB), and other regulatory factors in response to reactive oxygen species (ROS) and prostaglandin synthesis [27]. Furthermore, inhibition of AKR1B1 could render cancer cells more sensitive to anti-cancer therapy or alleviate the adverse effects of therapy.…”