Roles of AKR1C3 in malignancy

[1] In a previous study, Wang et al[2] demonstrated that AKR1C2 and AKR1C3 mediated the transformation of prostaglandin D2 (PGD2) to prostaglandin F2 (PGDF2), and then enhanced the proliferation of prostate cells via the activation of G-protein-coupled receptors for prostaglandin F2α (PGF2α) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway. AKR1C3 is known to induce an EMT phenotype in PCa cells both, in vitro and in vivo, by activating extracellular-regulated protein kinases (ERK) which then up-regulates various transcription factors zinc finger box-binding homeobox 1 (ZEB1), Twist family BHLHT transcription factor 1 (Twist1), and Slug. With regards to the relationship between AKR1C3 and urinary bladder carcinoma (UBC), Figueroa et al[12] reported a strong association between the risk of UBC and variations in genes that were involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines (AAs). [15] However, at least in leukemia, the inhibition of AKR1C3 alone is not enough to exert anti-leukemia effects. Because the leukemic properties of AML cells are consolidated by the combined activity of AKR1C1–AKR1C4 [Supplementary Table 1, http://links.lww.com/CM9/A460 and Figure 1].