Osteosarcoma (OS) is a sarcoma with high rates of pulmonary metastases and mortality. The mechanisms underlying tumour generation and development in OS are not well-understood. Haematopoietic cell kinase (HCK), a vital member of the Src family of kinase proteins, plays crucial roles in cancer progression and may act as an anticancer target; however, the mechanism by which HCK enhances OS development remains unexplored. Therefore, we investigated the role of HCK in OS development in vitro and in vivo. Downregulation of HCK attenuated OS cell proliferation, migration and invasion and increased OS cell apoptosis, whereas overexpression of HCK enhanced these processes. Mechanistically, HCK expression enhanced OS tumorigenesis via the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; HCK upregulation increased the phosphorylation of MEK and ERK and promoted epithelial-mesenchymal transition, with a reduction in E-cadherin in vitro. Furthermore, HCK downregulation decreased the tumour volume and weight in mice transplanted with OS cells. In conclusion, HCK plays a crucial role in OS tumorigenesis, progression and metastasis via the MEK/ERK pathway, suggesting that HCK is a potential target for developing treatments for OS.

中文翻译：

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造血细胞激酶通过 MEK/ERK 通路促进骨肉瘤的发展

骨肉瘤 (OS) 是一种具有高肺转移率和死亡率的肉瘤。OS中肿瘤产生和发展的机制尚不清楚。造血细胞激酶 (HCK) 是 Src 激酶蛋白家族的重要成员，在癌症进展中起关键作用，并可能作为抗癌靶点；然而，HCK 增强操作系统开发的机制仍未探索。因此，我们在体外和体内研究了 HCK 在 OS 发育中的作用。HCK 的下调减弱了 OS 细胞增殖、迁移和侵袭并增加了 OS 细胞凋亡，而 HCK 的过表达增强了这些过程。从机制上讲，HCK 表达通过丝裂原活化蛋白激酶 (MEK)/细胞外信号调节激酶 (ERK) 途径增强 OS 肿瘤发生；HCK 上调增加了 MEK 和 ERK 的磷酸化并促进了上皮-间质转化，体外 E-钙粘蛋白减少。此外，HCK 下调降低了移植 OS 细胞的小鼠的肿瘤体积和重量。总之，HCK 通过 MEK/ERK 通路在 OS 肿瘤发生、进展和转移中起关键作用，表明 HCK 是开发 OS 治疗的潜在靶点。