The phosphatase CTDSPL2 promotes proliferation, invasion, metastasis and regorafenib resistance in osteosarcoma

作者：Guannan Bai, Shaobo Zhao, Manli Zhao, Limiao Chen, Wenhao Chen · 发表于：Journal of bone oncology · 年份：2025 · DOI：10.1016/j.jbo.2025.100684 · 被引用次数：4 · 研究领域：PI3K/AKT/mTOR signaling in cancer、Biochemical and Molecular Research、Colorectal Cancer Treatments and Studies

• A systemic screen using regorafenib-treated osteosarcoma cell lines. • CTDSPL2 was found significantly up-regulated in regorafenib-treated osteosarcoma cell lines. • CTDSPL2 promoted osteosarcoma cell proliferation, invasion and metastasis while suppressing apoptosis in vitro. • CTDSPL2 was significantly up-regulated in osteosarcoma tissues compared with adjacent tissues. • CTDSPL2 is a potential therapeutic target for patients with osteosarcoma. Osteosarcoma is the most common bone malignancy in children and adolescents. Patients with metastatic and recurrent osteosarcoma have poor prognosis. Regorafenib is a multi-kinase inhibitor recommended as a complement to standard chemotherapy in the treatment of advanced osteosarcoma. The mechanisms associated with regorafenib resistance remains unclear. In this study we performed transcriptomics, proteomics and phosphorylated proteomics using regorafenib-treated osteosarcoma cell lines (MG-63, HOS-MNNG for transcriptomics, HOS-MNNG for proteomics and phosphorylated proteomics). After comprehensive multiomics and verification analyses of differentially expressed genes, essential genes for the malignancy of osteosarcoma cells were identified. The effects of essential genes on the proliferation, invasion, and migration of osteosarcoma were determined. The study also evaluated their role in the apoptosis of osteosarcoma cells. The up-regulation of essential genes was determined by immunohistochemistry assays. Using comprehensive multi...