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Chronic Stress Promotes Lung Adenocarcinoma Progression via α5-nAChR/FOXM1 Signaling Pathway
Jiaying Cai1, Zepeng Wang1, Tong Lu1
1Center for Basic and translational Medical Research, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Abstract:
The α5-nicotinic acetylcholine receptor (α5-nAChR) mediates chronic stress-induced lung adenocarcinoma (LUAD) progression. Forkhead Box M1 (FOXM1) is an oxidative stress-associated protein that is strongly associated with chronic stress and functions as a cancer-promoting transcription factor critical to LUAD. Our gene expression profiling demonstrated that CHRNA5 (encoding α5-nAChR) knockdown suppresses FOXM1 levels. It remains unknown whether and how α5-nAChR interacts with FOXM1 to promote chronic stress-induced LUAD progression. In this study, the expression and correlation of α5-nAChR and FOXM1 in LUAD of mice were investigated through chronic restraint stress (CRS). α5-nAChR expression was related to FOXM1 expression, low survival rate, staging, and smoking status in both LUAD dataset and tissue microarrays. In vitro experiments demonstrated that α5-nAChR mediates acetylcholine (ACh)-induced FOXM1, Ki67, and Sox2 expression via STAT3. α5-nAChR/FOXM1 signaling contributes to LUAD cell proliferation, migration, and invasion. Furthermore, α5-nAChR expression was linked to FOXM1 expression in chronic unpredictable mild stress (CUMS) mice tissues. The findings suggested that α5-nAChR/FOXM1 axis is involved in chronic stress-promoted LUAD progression.
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