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

The sodium pump alpha 3 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 alpha 3 subunit were positively associated with metastasis in colorectal cancer (CRC). Knockdown of the alpha 3 subunit or inhibition of the sodium pump could significantly inhibit the migration of colorectal cancer cells, whereas overexpression of the alpha 3 subunit promoted colorectal cancer cell migration. Mechanistically, the alpha 3 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 alpha 3 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 alpha 3 subunit expression and mTOR activity was observed in an aggressive CRC subtype. Conclusions: Elevated expression of the sodium pump alpha 3 subunit promotes CRC liver metastasis via the PTEN/IGFBP3-mediated mTOR pathway, suggesting that sodium pump alpha 3 could represent a critical prognostic marker and/or therapeutic target for this disease.

Automated summary

The study revealed that elevated expression of the sodium pump alpha 3 subunit is associated with colorectal cancer metastasis. Through mechanisms involving decreased p53 expression and activated mTOR pathway, the alpha 3 subunit promotes migration of colorectal cancer cells. Additionally, a positive correlation between alpha 3 subunit expression and mTOR activity was observed in an aggressive colorectal cancer subtype.