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

Wu，Di1; Yu，Hong Qiang1; Xiong，Hao Jun1; Zhang，Yu Jun1; Lin，Xiao Tong1; Zhang，Jie1; Wu，Wu1,2; Wang，Teng3; Liu，Xiao Yu3,4; Xie，Chuan Ming1

2021-11-12

10.3389/fonc.2021.743824

Frontiers in Oncology   影响因子和分区

2234-943X

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.

colorectal cancer IGFBP3 metastasis mTOR Na+/K+-ATPase p53 PTEN (phosphatase and tensin homolog deleted on chromosome 10)

SCI

英语

其他

WOS:000726112200001

2-s2.0-85120405956

Scopus

1.Key Laboratory of Hepatobiliary and Pancreatic Surgery,Institute of Hepatobiliary Surgery,Southwest Hospital,Third Military Medical University (Army Medical University),Chongqing,China
2.Department of Hepatobiliary Surgery,The Second Affiliated Hospital of Chongqing Medical University,Chongqing,China
3.Department of Oncology,Affiliated Hospital of Jiangnan University,Wuxi,China
4.School of Medicine,Southern University of Science and Technology,Shenzhen,China

Wu，Di,Yu，Hong Qiang,Xiong，Hao Jun,et al. Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis[J]. Frontiers in Oncology,2021,11.

Wu，Di.,Yu，Hong Qiang.,Xiong，Hao Jun.,Zhang，Yu Jun.,Lin，Xiao Tong.,...&Xie，Chuan Ming.(2021).Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis.Frontiers in Oncology,11.

Wu，Di,et al."Elevated Sodium Pump α3 Subunit Expression Promotes Colorectal Liver Metastasis via the p53-PTEN/IGFBP3-AKT-mTOR Axis".Frontiers in Oncology 11(2021).