CHAC1 in urological tumors: contextual dualism and therapeutic implications
CHAC1, a glutathione-degrading enzyme, governs context-dependent pathophysiological processes in urological malignancies through modulation of endoplasmic reticulum stress and ferroptotic pathways. In clear cell renal cell carcinoma (ccRCC), CHAC1 exhibits stage-specific functional duality: downregu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1610915/full |
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| author | Deyu Wang Yongquan Wan Yunxiang Li Yuan Ren Jiakai Ma Si Ge Ziqiang Zeng Zuoping Wang Lei Zhen |
| author_facet | Deyu Wang Yongquan Wan Yunxiang Li Yuan Ren Jiakai Ma Si Ge Ziqiang Zeng Zuoping Wang Lei Zhen |
| author_sort | Deyu Wang |
| collection | DOAJ |
| description | CHAC1, a glutathione-degrading enzyme, governs context-dependent pathophysiological processes in urological malignancies through modulation of endoplasmic reticulum stress and ferroptotic pathways. In clear cell renal cell carcinoma (ccRCC), CHAC1 exhibits stage-specific functional duality: downregulation in early-stage tumors correlates with adverse prognosis (suggesting tumor-suppressive activity), whereas elevated expression in advanced ccRCC (G3-G4/Stage III-IV) associates with increased mortality (indicating adaptive pro-survival adaptation). For prostate cancer, CHAC1 potentiates docetaxel cytotoxicity via coordinated induction of endoplasmic reticulum stress and ferroptosis, yet its suppression by cancer-associated fibroblast-derived exosomal miR-432-5p establishes therapy-reinforced chemoresistance. Mechanistically, CHAC1 intersects critical pathways by regulating redox homeostasis through glutathione catabolism, mediating potential crosstalk with androgen receptor signaling, and serving as an independent prognostic determinant in ccRCC (FPTOS_score model: HR = 2.028, 95% CI: 1.640-2.507). Notably, current evidence reveals no established link between CHAC1 and urothelial carcinoma pathogenesis. Further elucidation of CHAC1’s mechanistic intricacies and therapeutic targeting (e.g., CHAC1 agonists, exosomal miRNA antagonists) may advance precision management of urological tumors. |
| format | Article |
| id | doaj-art-e5a3115188e84be8a1d877d01a42d9dd |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e5a3115188e84be8a1d877d01a42d9dd2025-08-20T03:59:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16109151610915CHAC1 in urological tumors: contextual dualism and therapeutic implicationsDeyu WangYongquan WanYunxiang LiYuan RenJiakai MaSi GeZiqiang ZengZuoping WangLei ZhenCHAC1, a glutathione-degrading enzyme, governs context-dependent pathophysiological processes in urological malignancies through modulation of endoplasmic reticulum stress and ferroptotic pathways. In clear cell renal cell carcinoma (ccRCC), CHAC1 exhibits stage-specific functional duality: downregulation in early-stage tumors correlates with adverse prognosis (suggesting tumor-suppressive activity), whereas elevated expression in advanced ccRCC (G3-G4/Stage III-IV) associates with increased mortality (indicating adaptive pro-survival adaptation). For prostate cancer, CHAC1 potentiates docetaxel cytotoxicity via coordinated induction of endoplasmic reticulum stress and ferroptosis, yet its suppression by cancer-associated fibroblast-derived exosomal miR-432-5p establishes therapy-reinforced chemoresistance. Mechanistically, CHAC1 intersects critical pathways by regulating redox homeostasis through glutathione catabolism, mediating potential crosstalk with androgen receptor signaling, and serving as an independent prognostic determinant in ccRCC (FPTOS_score model: HR = 2.028, 95% CI: 1.640-2.507). Notably, current evidence reveals no established link between CHAC1 and urothelial carcinoma pathogenesis. Further elucidation of CHAC1’s mechanistic intricacies and therapeutic targeting (e.g., CHAC1 agonists, exosomal miRNA antagonists) may advance precision management of urological tumors.https://www.frontiersin.org/articles/10.3389/fonc.2025.1610915/fullCHAC1glutathione metabolismferroptosisendoplasmic reticulum stressprognostic biomarkerdrug resistance |
| spellingShingle | Deyu Wang Yongquan Wan Yunxiang Li Yuan Ren Jiakai Ma Si Ge Ziqiang Zeng Zuoping Wang Lei Zhen CHAC1 in urological tumors: contextual dualism and therapeutic implications Frontiers in Oncology CHAC1 glutathione metabolism ferroptosis endoplasmic reticulum stress prognostic biomarker drug resistance |
| title | CHAC1 in urological tumors: contextual dualism and therapeutic implications |
| title_full | CHAC1 in urological tumors: contextual dualism and therapeutic implications |
| title_fullStr | CHAC1 in urological tumors: contextual dualism and therapeutic implications |
| title_full_unstemmed | CHAC1 in urological tumors: contextual dualism and therapeutic implications |
| title_short | CHAC1 in urological tumors: contextual dualism and therapeutic implications |
| title_sort | chac1 in urological tumors contextual dualism and therapeutic implications |
| topic | CHAC1 glutathione metabolism ferroptosis endoplasmic reticulum stress prognostic biomarker drug resistance |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1610915/full |
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