CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis

Abstract Background Osteosarcoma (OS) patients with lung metastasis have poor prognoses, and effective therapeutic strategies for delaying or inhibiting the spread of lung metastasis from the primary OS site are lacking. Hence, it is critical to elucidate the underlying mechanisms of OS metastasis a...

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Autores principales:	Haoran Kong, Wenhui Yu, Zhuning Chen, Haonan Li, Guiwen Ye, Jiacong Hong, Zhongyu Xie, Keng Chen, Yanfeng Wu, Huiyong Shen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	CCR9 Lung metastasis Osteosarcoma Epithelial–mesenchymal transition Wnt/β-catenin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/396cb75ef4b44b0299f67f517dfe9bc1
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spelling	oai:doaj.org-article:396cb75ef4b44b0299f67f517dfe9bc12021-12-05T12:23:33ZCCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis10.1186/s12935-021-02320-01475-2867https://doaj.org/article/396cb75ef4b44b0299f67f517dfe9bc12021-12-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02320-0https://doaj.org/toc/1475-2867Abstract Background Osteosarcoma (OS) patients with lung metastasis have poor prognoses, and effective therapeutic strategies for delaying or inhibiting the spread of lung metastasis from the primary OS site are lacking. Hence, it is critical to elucidate the underlying mechanisms of OS metastasis and to identify additional new effective treatment strategies for patients. Methods Differential expression and functional analyses were performed to identify key genes and relevant signaling pathways associated with OS lung metastasis. The expression of CCR9 in OS cell lines and tissues was measured by RT-qPCR, western blotting and immunohistochemistry. Cell migration and invasion were assessed by wound healing and Transwell Matrigel invasion assays, respectively. The regulatory relationship between CCR9 and the Wnt/β-catenin signaling pathway was further evaluated by rescue experiments. Results The expression of CCR9 was elevated in OS cell lines and patients with lung metastasis. CCR9 promoted MG63 and HOS cell migration and invasion by activating the Wnt/β-catenin signaling pathway. Furthermore, knockdown of CCR9 repressed epithelial–mesenchymal transition (EMT) by downregulating mesenchymal markers (N-cadherin and Vimentin) and EMT-associated transcription factors (twist and snail) and upregulating an epithelial marker (E-cadherin). Conclusions Our findings suggest that CCR9 promotes EMT by activating Wnt/β-catenin pathways to promote OS metastasis. CCR9 may be a promising therapeutic target to inhibit lung metastasis and serve as a novel prognostic marker for OS.Haoran KongWenhui YuZhuning ChenHaonan LiGuiwen YeJiacong HongZhongyu XieKeng ChenYanfeng WuHuiyong ShenBMCarticleCCR9Lung metastasisOsteosarcomaEpithelial–mesenchymal transitionWnt/β-cateninNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CCR9 Lung metastasis Osteosarcoma Epithelial–mesenchymal transition Wnt/β-catenin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	CCR9 Lung metastasis Osteosarcoma Epithelial–mesenchymal transition Wnt/β-catenin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Haoran Kong Wenhui Yu Zhuning Chen Haonan Li Guiwen Ye Jiacong Hong Zhongyu Xie Keng Chen Yanfeng Wu Huiyong Shen CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
description	Abstract Background Osteosarcoma (OS) patients with lung metastasis have poor prognoses, and effective therapeutic strategies for delaying or inhibiting the spread of lung metastasis from the primary OS site are lacking. Hence, it is critical to elucidate the underlying mechanisms of OS metastasis and to identify additional new effective treatment strategies for patients. Methods Differential expression and functional analyses were performed to identify key genes and relevant signaling pathways associated with OS lung metastasis. The expression of CCR9 in OS cell lines and tissues was measured by RT-qPCR, western blotting and immunohistochemistry. Cell migration and invasion were assessed by wound healing and Transwell Matrigel invasion assays, respectively. The regulatory relationship between CCR9 and the Wnt/β-catenin signaling pathway was further evaluated by rescue experiments. Results The expression of CCR9 was elevated in OS cell lines and patients with lung metastasis. CCR9 promoted MG63 and HOS cell migration and invasion by activating the Wnt/β-catenin signaling pathway. Furthermore, knockdown of CCR9 repressed epithelial–mesenchymal transition (EMT) by downregulating mesenchymal markers (N-cadherin and Vimentin) and EMT-associated transcription factors (twist and snail) and upregulating an epithelial marker (E-cadherin). Conclusions Our findings suggest that CCR9 promotes EMT by activating Wnt/β-catenin pathways to promote OS metastasis. CCR9 may be a promising therapeutic target to inhibit lung metastasis and serve as a novel prognostic marker for OS.
format	article
author	Haoran Kong Wenhui Yu Zhuning Chen Haonan Li Guiwen Ye Jiacong Hong Zhongyu Xie Keng Chen Yanfeng Wu Huiyong Shen
author_facet	Haoran Kong Wenhui Yu Zhuning Chen Haonan Li Guiwen Ye Jiacong Hong Zhongyu Xie Keng Chen Yanfeng Wu Huiyong Shen
author_sort	Haoran Kong
title	CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
title_short	CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
title_full	CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
title_fullStr	CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
title_full_unstemmed	CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis
title_sort	ccr9 initiates epithelial–mesenchymal transition by activating wnt/β-catenin pathways to promote osteosarcoma metastasis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/396cb75ef4b44b0299f67f517dfe9bc1
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CCR9 initiates epithelial–mesenchymal transition by activating Wnt/β-catenin pathways to promote osteosarcoma metastasis

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