Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells

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 os...

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Autores principales:	Fei Peng, Haohuan Li, Jianping Li, Zhe Wang
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/33a909c054cb4faf8ca80e4f35e2f3a7
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spelling	oai:doaj.org-article:33a909c054cb4faf8ca80e4f35e2f3a72021-11-15T01:19:00ZDownregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells1942-099410.1155/2021/3672112https://doaj.org/article/33a909c054cb4faf8ca80e4f35e2f3a72021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/3672112https://doaj.org/toc/1942-0994Transmembrane 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.Fei PengHaohuan LiJianping LiZhe WangHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Fei Peng Haohuan Li Jianping Li Zhe Wang Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells
description	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.
format	article
author	Fei Peng Haohuan Li Jianping Li Zhe Wang
author_facet	Fei Peng Haohuan Li Jianping Li Zhe Wang
author_sort	Fei Peng
title	Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells
title_short	Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells
title_full	Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells
title_fullStr	Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells
title_full_unstemmed	Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells
title_sort	downregulation of the proton-activated cl- channel tmem206 inhibits malignant properties of human osteosarcoma cells
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/33a909c054cb4faf8ca80e4f35e2f3a7
work_keys_str_mv	AT feipeng downregulationoftheprotonactivatedclchanneltmem206inhibitsmalignantpropertiesofhumanosteosarcomacells AT haohuanli downregulationoftheprotonactivatedclchanneltmem206inhibitsmalignantpropertiesofhumanosteosarcomacells AT jianpingli downregulationoftheprotonactivatedclchanneltmem206inhibitsmalignantpropertiesofhumanosteosarcomacells AT zhewang downregulationoftheprotonactivatedclchanneltmem206inhibitsmalignantpropertiesofhumanosteosarcomacells
_version_	1718428975048425472

Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells

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