FGF-induced regulates the progression and metastasis of osteosarcoma via FRS2/TGF-β/β-catenin pathway.

Background: Fibroblast growth factor (FGF) and tumor growth factor-β (TGFβ) have emerged as pivotal regulators during the progression of osteosarcoma (OS). LHX9 is one crucial transcription factor controlled by FGF, however, its function in OS has not been investigated yet.

Methods: The expression of , , , -, , - and metastasis-related proteins was measured by real-time quantitative PCR (RT-qPCR) and Western blot. CCK-8 assay and colony formation assay were employed to determine the proliferation of OS cells, while scratch wound healing assay and transwell assay were used to evaluate their migration and invasion, respectively. In vivo tumor growth and metastasis were determined by subcutaneous or intravenous injection of OS cells into nude mice.

Results: expression was evidently up-regulated in OS tumor tissues and cell lines. Knockdown of impaired the proliferation, migration, invasion and metastasis of OS cells. Mechanistically, silencing led to the down-regulation of BMP-4, β-catenin and metastasis-related proteins, which was also observed in - knockdown OS cells. By contrast, knockdown conduced to the up-regulation of , BMP4, β-catenin and TGF-βR1, while - inhibition repressed the expression of and metastasis-related proteins. Additionally, - modulates and metastasis-related proteins by suppressing TGF- R1 expression on transcriptional level.

Conclusions: This study revealed was essential for the proliferation, migration, invasion, and metastasis of OS cells via FGF and TGF-β/β-catenin signaling pathways.