Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
Aging (Albany NY). 2024 Sep 6;16(17):12239-12251. doi: 10.18632/aging.206070.
The relationship between metastasis-associated protein 2 (MTA2) overexpression and tumor growth and metastasis has been extensively studied in a variety of tumor cells but not in human osteosarcoma cells. This study aims to elucidate the clinical significance, underlying molecular mechanisms, and biological functions of MTA2 in human osteosarcoma and . Our results show that MTA2 was elevated in osteosarcoma cell lines and osteosarcoma tissues and was associated with tumor stage and overall survival of osteosarcoma patients. Knockdown of MTA2 inhibited osteosarcoma cell migration and invasion by reducing the expression of urokinase-type plasminogen activator (uPA). Bioinformatic analysis demonstrated that high levels of uPA in human osteosarcoma tissues correlated positively with MTA2 expression. Furthermore, treatment with recombinant human uPA (Rh-uPA) caused significant restoration of OS cell migration and invasion in MTA2 knockdown osteosarcoma cells. We found that ERK1/2 depletion increased the expression of uPA, facilitating osteosarcoma cell migration and invasion. Finally, MTA2 depletion significantly reduced tumor metastasis and the formation of lung nodules . Overall, our study suggests that MTA2 knockdown suppresses osteosarcoma cell metastasis by decreasing uPA expression via ERK signaling. This finding provides new insight into potential treatment strategies against osteosarcoma metastasis by targeting MTA2.
转移相关蛋白 2（MTA2）过表达与肿瘤生长和转移之间的关系已在多种肿瘤细胞中得到广泛研究，但在人骨肉瘤细胞中尚未研究。本研究旨在阐明 MTA2 在人骨肉瘤中的临床意义、潜在分子机制和生物学功能。我们的结果表明，MTA2 在骨肉瘤细胞系和骨肉瘤组织中升高，并与骨肉瘤患者的肿瘤分期和总生存率相关。MTA2 的敲低通过降低尿激酶型纤溶酶原激活物（uPA）的表达抑制骨肉瘤细胞的迁移和侵袭。生物信息学分析表明，人骨肉瘤组织中高水平的 uPA 与 MTA2 表达呈正相关。此外，用重组人 uPA（Rh-uPA）处理导致 MTA2 敲低的骨肉瘤细胞中 OS 细胞迁移和侵袭的显著恢复。我们发现 ERK1/2 耗竭增加了 uPA 的表达，促进了骨肉瘤细胞的迁移和侵袭。最后，MTA2 的耗竭显著减少了肿瘤转移和肺结节的形成。总体而言，我们的研究表明，MTA2 的敲低通过 ERK 信号通路降低 uPA 表达抑制骨肉瘤细胞的转移。这一发现为通过靶向 MTA2 针对骨肉瘤转移的潜在治疗策略提供了新的见解。
