Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer

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

doi:10.1002/advs.202406688

journal article·2024-12Open access

Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer

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

Advanced Science· Volume 11· Issue 47

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Source abstract

Abstract

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.

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Research context

OpenAlex topics: Microtubule and mitosis dynamics · Ovarian cancer diagnosis and treatment · RNA Research and Splicing

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department 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 China

Department of Radiation Oncology Shenzhen Key Laboratory of Gastrointestinal Cancer Translational Research Peking University Shenzhen Hospital Shenzhen Guangdong 518036 China

Department 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 China

Department of Biochemistry Zhongshan School of Medicine Sun Yat‐sen University Guangzhou Guangdong 510060 China

Department 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 China

Department of Gynecologic Oncology The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital) Kunming Yunnan 650118 China

School of Medicine The Chinese University of Hong Kong Shenzhen Guangdong 518172 China

Department 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 China

Funding

National Key Research and Development Program of China · Natural Science Foundation of Guangdong Province · China Postdoctoral Science Foundation · Basic and Applied Basic Research Foundation of Guangdong Province · National Natural Science Foundation of China

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