Acid phosphatase type 6 promotes endometrial cancer progression via activating PI3K/AKT pathway

Abstract

Background: Endometrial cancer (EC) is one of the most prevalent malignant tumors affecting women's health and well-being, with both morbidity and mortality rates increasing every year. Acid phosphatase type 6 (ACP6) is a mitochondrial lipid phosphatase that is involved in tumorigenesis and cancer progression. Although ACP6 is significantly contributing to these pathways, its specific function in EC remains poorly explored.

Methods: RNA-Seq files of EC tissue and normal endometrial tissue were obtained from The Cancer Genome Atlas (TCGA). ACP6 expression was assessed using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot. The impact of ACP6 overexpression or silencing on EC cell proliferation, migration, and invasion was evaluated using lentivirus-transfected EC cell lines, measured by cell counting kit 8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, and Transwell assay. In vivo experiments were performed using stable HEC-1A cells with ACP6 knockdown to evaluate tumorigenicity. Cellular RNA-seq and western blotting were performed to detect the activation of the PI3K/AKT signaling pathway.

Results: ACP6 expression in EC tissue was significantly higher than that in normal endometrial tissue. ACP6 overexpression in vitro increased the proliferation, migration, and invasion of EC cells while ACP6 silencing decreased these effects. PI3K/AKT signaling pathway was inhibited after ACP6 knockdown. ACP6 knockdown significantly inhibited tumor growth in vivo in nude mice.

Conclusions: ACP6 might facilitate the development of EC through PI3K/AKT signaling pathway activation, potentially offering a new and promising therapeutic target for EC treatment.

Keywords: Acid phosphatase type 6; Endometrial cancer; PI3K/AKT pathway.