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钠泵α3亚基表达升高通过p53-PTEN/IGFBP3-AKT-mTOR轴促进结直肠癌肝转移

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

作者信息

Wu Di, Yu Hong-Qiang, Xiong Hao-Jun, Zhang Yu-Jun, Lin Xiao-Tong, Zhang Jie, Wu Wu, Wang Teng, Liu Xiao-Yu, Xie Chuan-Ming

机构信息

Key Laboratory of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Oncol. 2021 Nov 12;11:743824. doi: 10.3389/fonc.2021.743824. eCollection 2021.

DOI:10.3389/fonc.2021.743824
PMID:34868940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8632823/
Abstract

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 and the downregulation of mTOR activity. Furthermore, a positive correlation between α3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Elevated expression of the sodium pump α3 subunit promotes CRC liver metastasis the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump α3 could represent a critical prognostic marker and/or therapeutic target for this disease.

摘要

钠泵α3亚基与结直肠癌肝转移相关。然而，这种作用所涉及的潜在机制尚不清楚。在本研究中，我们发现钠泵α3亚基的表达水平与结直肠癌（CRC）的转移呈正相关。敲低α3亚基或抑制钠泵可显著抑制结直肠癌细胞的迁移，而α3亚基的过表达则促进结直肠癌细胞迁移。机制上，α3亚基降低p53表达，随后下调PTEN/IGFBP3并激活mTOR，从而促进结直肠癌细胞转移。相反，敲低α3亚基或抑制钠泵可显著阻断这种效应以及mTOR活性的下调。此外，在侵袭性CRC亚型中观察到α3亚基表达与mTOR活性之间呈正相关。钠泵α3亚基的表达升高通过PTEN/IGFBP3介导的mTOR途径促进CRC肝转移，这表明钠泵α3可能是该疾病的关键预后标志物和/或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/0e10f6f41fbb/fonc-11-743824-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/2fb60831d289/fonc-11-743824-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/8fa2a7981c4d/fonc-11-743824-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/ebde6277c938/fonc-11-743824-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/ae8c09a8894e/fonc-11-743824-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/7e8f41948188/fonc-11-743824-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/0e10f6f41fbb/fonc-11-743824-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/2fb60831d289/fonc-11-743824-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/8fa2a7981c4d/fonc-11-743824-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/ebde6277c938/fonc-11-743824-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/ae8c09a8894e/fonc-11-743824-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/7e8f41948188/fonc-11-743824-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/8632823/0e10f6f41fbb/fonc-11-743824-g006.jpg

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