SLC39A14 promotes the development of esophageal squamous cell carcinoma through PI3K/Akt/mTOR signaling pathway

This study aims to investigate the expression of solute carrier family 39 member 14 (SLC39A14) in esophageal squamous cell carcinoma (ESCC) tissues and its prognosis, as well as the impact of SLC39A14 expression on the biological behavior of ESCC cells and associated mechanisms.

Bioinformatics analysis was utilized to compare the differential expression of SLC39A14 mRNA between esophageal cancer tissues and adjacent non-cancerous tissues. Immunohistochemistry was employed to evaluate SLC39A14 protein expression in human ESCC tissues and normal esophageal tissues, followed by an analysis of its association with clinicopathological parameters in esophageal cancer patients. Through cell proliferation, migration, invasion, and Western blot assays, we deeply evaluated the specific effects of SLC39A14 gene knockdown (or overexpression) on ESCC cells and explored its potential biological functions in ESCC. Subsequently, we validated the role of SLC39A14 in ESCC in a xenograft model. Furthermore, LY294002 drug intervention was used to verify the regulatory effect of SLC39A14 on PI3K/Akt/mTOR signaling pathway.

Both mRNA and protein levels of SLC39A14 were significantly elevated in tumor tissues from ESCC patients compared to adjacent normal tissues. Notably, higher levels of SLC39A14 expression positively correlated with ESCC tumor size (p = 0.010) and clinical T stage (p = 0.025), while exhibiting a negative correlation with overall patient survival rates (p = 0.023). In vitro experiments demonstrated that knocking down SLC39A14 significantly inhibited cell proliferation, migration and invasion. In vivo study showed that SLC39A14 facilitated progression within murine models bearing ESCC tumors. Mechanistic analyses suggested that pro-carcinogenic effects exerted by SLC39A14 are mediated through activation of the PI3K/Akt/mTOR signaling pathway.

Our findings suggest that SLC39A14 may serve as a potential biomarker for ESCC due to its pro-oncogenic role during ESCC progression.