Background: Osteosarcoma is an aggressive bone tumor with a high risk of lung metastasis, which severely affects patient survival. EMT plays a major role in tumor spread, therapy resistance, and cancer stemness. This review explores how EMT contributes to osteosarcoma metastasis and the underlying molecular mechanisms. Methods: We reviewed recent studies on EMT-related signaling pathways, transcription factors, and regulatory RNAs in osteosarcoma. We also examined the role of the tumor microenvironment. Results: EMT promotes cell detachment, migration, and lung colonization. Key pathways such as TGF-β, MAPK, PI3K/Akt, STAT3, Notch, and Wnt/β-catenin are involved. Non-coding RNAs further regulate EMT by interacting with these pathways. The tumor microenvironment, including hypoxia and immune cells, also supports EMT and metastasis. Conclusions: EMT is a key driver of metastasis and poor outcomes in osteosarcoma. Targeting EMT and its regulators may help prevent lung spread and improve treatment. Future strategies combining EMT inhibition with existing therapies could be promising for clinical application.
背景：骨肉瘤是一种侵袭性骨肿瘤，具有较高的肺转移风险，严重影响患者生存。上皮间质转化在肿瘤扩散、治疗抵抗和癌症干细胞特性中起主要作用。本综述探讨了上皮间质转化如何促进骨肉瘤转移及其潜在的分子机制。方法：我们回顾了近年来关于骨肉瘤中上皮间质转化相关信号通路、转录因子和调控性RNA的研究，并探讨了肿瘤微环境的作用。结果：上皮间质转化促进细胞脱离、迁移和肺定植。关键通路如TGF-β、MAPK、PI3K/Akt、STAT3、Notch和Wnt/β-catenin参与其中。非编码RNA通过与这些通路相互作用进一步调控上皮间质转化。肿瘤微环境（包括缺氧和免疫细胞）也支持上皮间质转化和转移过程。结论：上皮间质转化是骨肉瘤转移和不良预后的关键驱动因素。靶向上皮间质转化及其调控因子可能有助于预防肺转移并改善治疗效果。未来将上皮间质转化抑制与现有疗法相结合的策略在临床应用中具有广阔前景。
Epithelial–Mesenchymal Transition in Osteosarcoma as a Key Driver of Pulmonary Metastasis
肿瘤(癌症)患者之家