Work

TRIM47 Facilitates Osteosarcoma Progression via Destabilising FBP1 and Thus Activation of Wnt/β‐Catenin Pathway

Year: 2025

Type: article

Abstract: Osteosarcoma is a malignant bone tumour with a high rate of disability and mortality in adolescents. Tripartite motif containing 47 (TRIM47) upregulation contributed greatly to carcinogenesis and progression in several tumours, while its role in osteosarcoma (OS) is still unclear and needs further investigation. In this study, we first evidenced that TRIM47 was frequently upregulated in osteosarcoma tissues and cell lines, and the higher TRIM47 expression predicted poor outcomes for osteosarcoma patients. Moreover, TRIM47 depletion impeded cell proliferation, migration, and invasion of osteosarcoma cells, while TRIM47 overexpression elicited opposite effects. Mechanistically, TRIM47 interacted with and accelerated the degradation of fructose 1, 6-bisphosphatase 1 (FBP1) by inducing its ubiquitination, subsequently activating the Wnt/β-catenin signalling pathway. Furthermore, knockdown of FBP1 reversed the functions of TRIM47 depletion in OS cells. More notably, our in vivo assays showed that loss of TRIM47 slowed the growth rate of osteosarcoma xenograft tumours. Overall, our data indicated that TRIM47 facilitates OS progression by promoting proteasomal degradation of FBP1, thereby activating the Wnt/β-catenin pathway, which clarified that targeting the TRIM47-FBP1-β-catenin axis could be a promising approach for treating OS.

Source: Journal of Cellular and Molecular Medicine

DOI: 10.1111/jcmm.70753