Abstract
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.
Highlights
Osteosarcoma (OS) is the most common primary aggressive and malignant tumor of the bone, with high morbidity and metastatic potential
We present evidence to demonstrate Transmembrane protein 206 (TMEM206) role in OS development and its potential regulatory pathway
Taking advantage of clinical specimens and wellcharacterized OS cell lines, we sought to establish whether TMEM206 is associated with OS pathogenesis
Summary
Osteosarcoma (OS) is the most common primary aggressive and malignant tumor of the bone, with high morbidity and metastatic potential. 75% of OS patients are between 15 and 25 years of age, which heavily threatens the health of adolescents [1]. Significant progress has been made in diagnostic and therapeutic methods, the primary treatment for OS mainly depends on surgery combined with adjuvant chemotherapy; the clinical outcome is unsatisfactory [2]. The five-year survival rate of osteosarcoma without metastasis is only 60-70% [3]. Metastasis is common in OS, and approximately 85% of metastases are located in lungs [4], which contributes to most patients’ death. Exploring efficient diagnostic biomarkers and therapeutic targets for HCC treatment could lead to novel intervention strategies for improving OS clinical outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
