GPD1L may inhibit the development of esophageal squamous cell carcinoma through the PI3K/AKT signaling pathway: bioinformatics analysis and experimental exploration.

Background: Esophageal squamous carcinoma (ESCC) is the most prevalent pathological subtype of esophageal cancer (EC). It has the characteristics of significant local invasion, quick disease progression, high recurrence rates, and a dismal prognosis for survival. Phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) is a signaling system whose aberrant activation regulates downstream factors, leading to the promotion of cancer development. This study looks at a protein called Glycerol-3-phosphate dehydrogenase 1-like (GPD1L), which strongly affects the development of several cancers. However, its association with ESCC development and its underlying mechanisms are not clear.

Methods: In this paper, we analyzed six ESCC transcriptome data obtained from the GEO database. We utilized bioinformatics technology and immunohistochemistry to differentially analyze GPD1L levels of mRNA and protein expression in ESCC and normal adjacent tissues. Furthermore, we conducted survival, co-expression, enrichment, immune infiltration and drug sensitivity analysis. Moreover, we further investigated the role and mechanism of GPD1L by Western Blot (WB), Cell Counting Kit-8 (CCK8), wound healing assay, Transwell assay, and flow cytometry. Finally, the addition of IGF-1, the activator of PI3K/AKT, could rescue the inhibitory effect of GPD1L on ESCC.

Results: The findings manifest that the expression of GPD1L was low in ESCC, and functional experiments showed that GPD1L promoted apoptosis in vitro while blocking cell migration, invasion, and proliferation. Based on mechanism research, GPD1L's impact on ESCC could be explained by its suppression of the PI3K/AKT signaling pathway's activation.

Conclusion: To sum up, our findings imply that GPD1L may impede the initiation and advancement of ESCC via modulating the PI3K/AKT signaling pathway. GPD1L is considered to be a promising therapeutic target and biomarker to diagnose and treat ESCC.