Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer
Abstract In epithelial ovarian cancer (EOC), platinum resistance, potentially mediated by cancer stem cells (CSCs), often leads to relapse and treatment failure. Here, the role of spindle pole body component 25 (SPC25) as a key determinant promoting stemness and platinum resistance in EOC cells, wit...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406688 |
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| author | Xingyu Jiang Muwen Yang Weijing Zhang Dongni Shi Yue Li Lixin He Shumei Huang Boyu Chen Xuwei Chen Lingzhi Kong Yibing Pan Pinwei Deng Rui Wang Ying Ouyang Xiangfu Chen Jun Li Zheng Li Hequn Zou Yanna Zhang Libing Song |
| author_facet | Xingyu Jiang Muwen Yang Weijing Zhang Dongni Shi Yue Li Lixin He Shumei Huang Boyu Chen Xuwei Chen Lingzhi Kong Yibing Pan Pinwei Deng Rui Wang Ying Ouyang Xiangfu Chen Jun Li Zheng Li Hequn Zou Yanna Zhang Libing Song |
| author_sort | Xingyu Jiang |
| collection | DOAJ |
| description | Abstract In epithelial ovarian cancer (EOC), platinum resistance, potentially mediated by cancer stem cells (CSCs), often leads to relapse and treatment failure. Here, the role of spindle pole body component 25 (SPC25) as a key determinant promoting stemness and platinum resistance in EOC cells, with its expression being correlated with adverse clinical outcomes is delineated. Mechanistically, SPC25 acts as a scaffolding platform, orchestrating the assembly of an SPC25/RIOK1/MYH9 trimeric complex, triggering RIOK1‐mediated phosphorylation of MYH9 at Ser1943. This prompts MYH9 to disengage from the cytoskeleton, augmenting its nuclear accumulation, thus potentiating CTNNB1 transcription and subsequent activation of Wnt/β‐catenin signaling. CBP1, a competitive inhibitory peptide, can disrupt the formation of the aforementioned trimeric complex, diminishing the activity of the SPC25/RIOK1/MYH9 axis–mediated Wnt/β‐catenin signaling, and thus attenuate CSC phenotypes, thereby enhancing platinum efficacy in vitro, in vivo, and in patient‐derived organoids. Therefore, targeting the SPC25/RIOK1/MYH9 axis, which mediates the maintenance of stemness and platinum resistance in EOC cells, may enhance platinum sensitivity and increase survival in patients with EOC. |
| format | Article |
| id | doaj-art-1503d513de4c4be29beef0a3bde1ed9b |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-1503d513de4c4be29beef0a3bde1ed9b2025-08-20T01:58:42ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202406688Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian CancerXingyu Jiang0Muwen Yang1Weijing Zhang2Dongni Shi3Yue Li4Lixin He5Shumei Huang6Boyu Chen7Xuwei Chen8Lingzhi Kong9Yibing Pan10Pinwei Deng11Rui Wang12Ying Ouyang13Xiangfu Chen14Jun Li15Zheng Li16Hequn Zou17Yanna Zhang18Libing Song19Department of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Radiation Oncology Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research Peking University Shenzhen Hospital Shenzhen Guangdong 518036 ChinaDepartment of Radiology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Biochemistry Zhongshan School of Medicine Sun Yat‐sen University Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Pathology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Biochemistry Zhongshan School of Medicine Sun Yat‐sen University Guangzhou Guangdong 510060 ChinaDepartment of Gynecologic Oncology The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital) Kunming Yunnan 650118 ChinaSchool of Medicine The Chinese University of Hong Kong Shenzhen Guangdong 518172 ChinaDepartment of Gynecology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Experimental Research State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou Guangdong 510060 ChinaAbstract In epithelial ovarian cancer (EOC), platinum resistance, potentially mediated by cancer stem cells (CSCs), often leads to relapse and treatment failure. Here, the role of spindle pole body component 25 (SPC25) as a key determinant promoting stemness and platinum resistance in EOC cells, with its expression being correlated with adverse clinical outcomes is delineated. Mechanistically, SPC25 acts as a scaffolding platform, orchestrating the assembly of an SPC25/RIOK1/MYH9 trimeric complex, triggering RIOK1‐mediated phosphorylation of MYH9 at Ser1943. This prompts MYH9 to disengage from the cytoskeleton, augmenting its nuclear accumulation, thus potentiating CTNNB1 transcription and subsequent activation of Wnt/β‐catenin signaling. CBP1, a competitive inhibitory peptide, can disrupt the formation of the aforementioned trimeric complex, diminishing the activity of the SPC25/RIOK1/MYH9 axis–mediated Wnt/β‐catenin signaling, and thus attenuate CSC phenotypes, thereby enhancing platinum efficacy in vitro, in vivo, and in patient‐derived organoids. Therefore, targeting the SPC25/RIOK1/MYH9 axis, which mediates the maintenance of stemness and platinum resistance in EOC cells, may enhance platinum sensitivity and increase survival in patients with EOC.https://doi.org/10.1002/advs.202406688cancer stem cellcell‐penetrating peptideepithelial ovarian cancerphosphorylationplatinum resistanceprotein‐protein interaction |
| spellingShingle | Xingyu Jiang Muwen Yang Weijing Zhang Dongni Shi Yue Li Lixin He Shumei Huang Boyu Chen Xuwei Chen Lingzhi Kong Yibing Pan Pinwei Deng Rui Wang Ying Ouyang Xiangfu Chen Jun Li Zheng Li Hequn Zou Yanna Zhang Libing Song Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer Advanced Science cancer stem cell cell‐penetrating peptide epithelial ovarian cancer phosphorylation platinum resistance protein‐protein interaction |
| title | Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer |
| title_full | Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer |
| title_fullStr | Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer |
| title_full_unstemmed | Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer |
| title_short | Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer |
| title_sort | targeting the spc25 riok1 myh9 axis to overcome tumor stemness and platinum resistance in epithelial ovarian cancer |
| topic | cancer stem cell cell‐penetrating peptide epithelial ovarian cancer phosphorylation platinum resistance protein‐protein interaction |
| url | https://doi.org/10.1002/advs.202406688 |
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