1 research outputs found
Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and TumorâAssociated Macrophages in Prostate Cancer
Abstract Tumorâassociated macrophages (TAMs) play an essential role in tumor therapeutic resistance. Although the lethal effect of ferroptosis on tumor cells is well reported, how TAMs inhibit the effect of ferroptosis in tumors has not been clearly defined. In this study, it is demonstrated that TAMâsecreted taurine suppresses ferroptosis in prostate cancer (PCa) by activating the Liver X receptor alpha/StearoylâCoenzyme A desaturase 1 (LXRα/SCD1) pathway. Blocking taurine intake via inhibition of taurine transporter TauT restores the sensitivity to ferroptosis in tumors. Furthermore, LXRα activates the transcription of both miRâ181aâ5p and its binding protein FUS to increase the recruitment of miRâ181aâ5p in tumorâderived extracellular vesicles (EVs). It is observed that macrophages appear to be recipient cells of the miRâ181aâ5pâenriched EVs. Intake of miRâ181aâ5p in macrophages promotes their M2 polarization and enhances the taurine export by inhibiting expression of its target gene lats1, which in turn inactivates the hippo pathway and results in a Yesâassociated protein (YAP) nuclear translocation for transcriptional activation of both M2 polarizationârelated genes such as ARG1 and CD163 and the taurine transport gene TauT. Taken together, the findings indicate a reciprocal interaction between PCa cells and TAMs as a positive feedbackâloop to repress ferroptosis in PCa, mediated by TAMâsecreted taurine and tumor EVâdelivered miRâ181aâ5p