MTA2 knockdown suppresses human osteosarcoma metastasis by inhibiting uPA expression

TL;DR

This study shows that reducing MTA2 in osteosarcoma cells decreases metastasis by lowering uPA levels, offering a potential new treatment strategy.

Contribution

The study reveals a novel mechanism by which MTA2 promotes osteosarcoma metastasis through uPA and ERK signaling.

Findings

MTA2 is overexpressed in osteosarcoma and correlates with tumor stage and survival.

MTA2 knockdown reduces cell migration and invasion by inhibiting uPA expression.

ERK1/2 depletion increases uPA, promoting metastasis, which is reversed by MTA2 depletion.

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.

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