Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer
Abstract Tumor‐associated 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 TA...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202303894 |
| _version_ | 1827378696600682496 |
|---|---|
| author | Huixiang Xiao Xinxing Du Zhenkeke Tao Nan Jing Shijia Bao Wei‐Qiang Gao Baijun Dong Yu‐Xiang Fang |
| author_facet | Huixiang Xiao Xinxing Du Zhenkeke Tao Nan Jing Shijia Bao Wei‐Qiang Gao Baijun Dong Yu‐Xiang Fang |
| author_sort | Huixiang Xiao |
| collection | DOAJ |
| description | Abstract Tumor‐associated 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 TAM‐secreted taurine suppresses ferroptosis in prostate cancer (PCa) by activating the Liver X receptor alpha/Stearoyl‐Coenzyme 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 miR‐181a‐5p and its binding protein FUS to increase the recruitment of miR‐181a‐5p in tumor‐derived extracellular vesicles (EVs). It is observed that macrophages appear to be recipient cells of the miR‐181a‐5p‐enriched EVs. Intake of miR‐181a‐5p 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 Yes‐associated protein (YAP) nuclear translocation for transcriptional activation of both M2 polarization‐related 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 feedback‐loop to repress ferroptosis in PCa, mediated by TAM‐secreted taurine and tumor EV‐delivered miR‐181a‐5p. |
| first_indexed | 2024-03-08T13:00:37Z |
| format | Article |
| id | doaj.art-b479b940159e4e8bbbc5e81ded64ad91 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T13:00:37Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-b479b940159e4e8bbbc5e81ded64ad912024-01-19T09:27:54ZengWileyAdvanced Science2198-38442024-01-01113n/an/a10.1002/advs.202303894Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate CancerHuixiang Xiao0Xinxing Du1Zhenkeke Tao2Nan Jing3Shijia Bao4Wei‐Qiang Gao5Baijun Dong6Yu‐Xiang Fang7State Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaDepartment of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaState Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaSchool of Biomedical Engineering and Med‐X Research Institute Shanghai Jiao Tong University Shanghai 200030 P. R. ChinaState Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaState Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaDepartment of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaState Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 P. R. ChinaAbstract Tumor‐associated 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 TAM‐secreted taurine suppresses ferroptosis in prostate cancer (PCa) by activating the Liver X receptor alpha/Stearoyl‐Coenzyme 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 miR‐181a‐5p and its binding protein FUS to increase the recruitment of miR‐181a‐5p in tumor‐derived extracellular vesicles (EVs). It is observed that macrophages appear to be recipient cells of the miR‐181a‐5p‐enriched EVs. Intake of miR‐181a‐5p 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 Yes‐associated protein (YAP) nuclear translocation for transcriptional activation of both M2 polarization‐related 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 feedback‐loop to repress ferroptosis in PCa, mediated by TAM‐secreted taurine and tumor EV‐delivered miR‐181a‐5p.https://doi.org/10.1002/advs.202303894extracellular vesiclesferroptosisprostate cancertaurinetumor‐associated macrophages |
| spellingShingle | Huixiang Xiao Xinxing Du Zhenkeke Tao Nan Jing Shijia Bao Wei‐Qiang Gao Baijun Dong Yu‐Xiang Fang Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer Advanced Science extracellular vesicles ferroptosis prostate cancer taurine tumor‐associated macrophages |
| title | Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer |
| title_full | Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer |
| title_fullStr | Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer |
| title_full_unstemmed | Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer |
| title_short | Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer |
| title_sort | taurine inhibits ferroptosis mediated by the crosstalk between tumor cells and tumor associated macrophages in prostate cancer |
| topic | extracellular vesicles ferroptosis prostate cancer taurine tumor‐associated macrophages |
| url | https://doi.org/10.1002/advs.202303894 |
| work_keys_str_mv | AT huixiangxiao taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT xinxingdu taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT zhenkeketao taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT nanjing taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT shijiabao taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT weiqianggao taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT baijundong taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer AT yuxiangfang taurineinhibitsferroptosismediatedbythecrosstalkbetweentumorcellsandtumorassociatedmacrophagesinprostatecancer |