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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Published in | Frontiers in oncology Vol. 11; p. 743824 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
12.11.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Yuming Jiang, Stanford University, United States This article was submitted to Gastrointestinal Cancers: Colorectal Cancer, a section of the journal Frontiers in Oncology These authors have contributed equally to this work Reviewed by: Devanjan Sinha, Banaras Hindu University, India; Lei Zhang, Sun Yat-sen University, China; Zhengshui Xu, The First Affiliated Hospital of Xi’an Jiaotong University, China |
ISSN: | 2234-943X 2234-943X |
DOI: | 10.3389/fonc.2021.743824 |