Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis

The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC...

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Autores principales:	Di Wu, Hong-Qiang Yu, Hao-Jun Xiong, Yu-Jun Zhang, Xiao-Tong Lin, Jie Zhang, Wu Wu, Teng Wang, Xiao-Yu Liu, Chuan-Ming Xie
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	colorectal cancer metastasis Na+/K+-ATPase mTOR p53 PTEN (phosphatase and tensin homolog deleted on chromosome 10) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/7776092030c84bd58743d561dfa6b0f1
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spelling	oai:doaj.org-article:7776092030c84bd58743d561dfa6b0f12021-11-12T05:06:42ZElevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis2234-943X10.3389/fonc.2021.743824https://doaj.org/article/7776092030c84bd58743d561dfa6b0f12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.743824/fullhttps://doaj.org/toc/2234-943XThe sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.Di WuHong-Qiang YuHao-Jun XiongYu-Jun ZhangXiao-Tong LinJie ZhangWu WuWu WuTeng WangXiao-Yu LiuXiao-Yu LiuChuan-Ming XieFrontiers Media S.A.articlecolorectal cancermetastasisNa+/K+-ATPasemTORp53PTEN (phosphatase and tensin homolog deleted on chromosome 10)Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	colorectal cancer metastasis Na+/K+-ATPase mTOR p53 PTEN (phosphatase and tensin homolog deleted on chromosome 10) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	colorectal cancer metastasis Na+/K+-ATPase mTOR p53 PTEN (phosphatase and tensin homolog deleted on chromosome 10) Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Di Wu Hong-Qiang Yu Hao-Jun Xiong Yu-Jun Zhang Xiao-Tong Lin Jie Zhang Wu Wu Wu Wu Teng Wang Xiao-Yu Liu Xiao-Yu Liu Chuan-Ming Xie Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
description	The sodium pump α3 subunit is associated with colorectal liver metastasis. However, the underlying mechanism involved in this effect is not yet known. In this study, we found that the expression levels of the sodium pump α3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the α3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the α3 subunit promoted colorectal cancer cell migration. Mechanistically, the α3 subunit decreased p53 expression, which subsequently downregulated PTEN/IGFBP3 and activated mTOR, leading to the promotion of colorectal cancer cell metastasis. Reciprocally, knockdown of the α3 subunit or inhibition of the sodium pump dramatically blocked this effect in vitro and in vivo via the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.
format	article
author	Di Wu Hong-Qiang Yu Hao-Jun Xiong Yu-Jun Zhang Xiao-Tong Lin Jie Zhang Wu Wu Wu Wu Teng Wang Xiao-Yu Liu Xiao-Yu Liu Chuan-Ming Xie
author_facet	Di Wu Hong-Qiang Yu Hao-Jun Xiong Yu-Jun Zhang Xiao-Tong Lin Jie Zhang Wu Wu Wu Wu Teng Wang Xiao-Yu Liu Xiao-Yu Liu Chuan-Ming Xie
author_sort	Di Wu
title	Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
title_short	Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
title_full	Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
title_fullStr	Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
title_full_unstemmed	Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis
title_sort	elevated sodium pump α3 subunit expression promotes colorectal liver metastasis via the p53-pten/igfbp3-akt-mtor axis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7776092030c84bd58743d561dfa6b0f1
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Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis

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