Research Paper Volume 16, Issue 17 pp 12239—12251
MTA2 knockdown suppresses human osteosarcoma metastasis by inhibiting uPA expression
- 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- 2 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
- 3 Spine Center, China Medical University Hospital, Taichung, Taiwan
- 4 Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
- 5 Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
- 6 Department of Leisure Industry Management, National Chin-Yi University of Technology, Taichung, Taiwan
- 7 Department of Biomedical Sciences National Chung Cheng University, Chiayi, Taiwan
- 8 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- 9 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
- 10 Department of Orthopedics, Chung Shan Medical University Hospital, Taichung, Taiwan
- 11 School of Medicine, Chung Shan Medical University, Taichung, Taiwan
Received: February 23, 2024 Accepted: July 17, 2024 Published: September 6, 2024
https://doi.org/10.18632/aging.206070How to Cite
Copyright: © 2024 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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 in vitro and in vivo. 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 in vivo. 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.