HSPE1 enhances aerobic glycolysis to promote progression of lung adenocarcinoma

Objective: This study aimed to explore the role of heat shock protein family E member 1 (HSPE1) in the metabolism of lung adenocarcinoma (LUAD) cells. Methods: Bioinformatics analysis was applied to examine the expression of HSPE1 in LUAD and its correlation with patient survival. Single-gene Gene Set Enrichment Analysis was conducted for HSPE1. LUAD cell lines or mouse models with up-regulated/down-regulated HSPE1 were constructed. The expression level of HSPE1 was detected by qRT-PCR or immunohistochemical staining. We used CCK-8 assay to measure cell viability and flow cytometry to detect apoptosis levels. Transwell assay was performed to evaluate migration and invasion characteristics. Extracellular Flux Analyzer was employed to detect oxygen consumption rate and extracellular acidification rate. Glucose consumption, adenosine triphosphate production, and lactate levels were measured by Reagent kits. Western blot analysis was conducted to examine the expression levels of GLUT1, HK2, and LDHA. Results: HSPE1 promoted proliferative, migratory, and invasive abilities, and inhibited apoptosis of LUAD cells through the aerobic glycolysis pathway. Specifically, LUAD cells with HSPE1 knockdown exhibited significantly decreased proliferation, migration, and invasion abilities, along with an increased apoptosis rate. Additionally, the expression levels of aerobic glycolysis-related proteins HK2, LADH, and GLUT1 were downregulated, while their levels were increased in LUAD cells with high HSPE1 expression. Suppression of aerobic glycolysis by 2-DG attenuated the promoting effects of HSPE1 overexpression on the proliferation, migration, and invasion of LUAD cells. HSPE1 knockdown inhibited tumor growth and decreased expression levels of HK2, LADH, and GLUT1 in vivo. Conclusion: HSPE1 regulated the proliferation, migration, and invasion of LUAD cells through the aerobic glycolysis pathway, thus facilitating malignant development of LUAD. The study suggested that HSPE1 could be useful as a therapeutic target for LUAD.