Transmembrane
protein 206 (TMEM206), a
proton-activated
chloride channel, has been implicated in various biochemical processes, including bone metabolism, and has emerged as a novel
cancer-related
protein in multiple
tumor types. However, its role in primary malignant bone
tumors, particularly in
osteosarcoma (OS), remains unclear. This study is aimed at exploring the effects of TMEM206 gene silencing on the proliferation, migration, invasion, and
metastasis of human OS cells in vitro and in vivo using an
shRNA-knockdown strategy. We found that TMEM206 is frequently overexpressed and that high levels of TMEM206 correlated with clinical stage and pulmonary
metastasis in patients with OS. We provided evidence that TMEM206-silenced OS
cancer cells exhibit decreased proliferation, migration, and invasion in vitro. Mechanistically, we identified β-
catenin, a key member of Wnt/β-
catenin signaling, as a downstream effector of TMEM206. TMEM206 silencing inhibits the Wnt/β-
catenin signaling pathway in expression rescue experiments, confirming that TMEM206 silencing attenuates OS cell tumorigenic behavior, at least in part, via the β-
catenin mediated downregulation of Wnt/β-
catenin signaling. More importantly, TMEM206 knockdown-related phenotype changes were replicated in a xenograft nude mouse model where pulmonary
metastases of OS cells were suppressed. Together, our results demonstrate that silencing TMEM206 negatively modulates the Wnt/β-
catenin signaling pathway via β-
catenin to suppress proliferation, migration, invasion, and
metastasis in OS
carcinogenesis, suggesting TMEM206 as a potential oncogenic
biomarker and a potential target for OS treatment.