中国病理生理杂志2026，Vol.42Issue(5)：875-883,9.DOI:10.3969/j.issn.1000-4718.2026.05.005
HSPA4诱导内质网应激激活β-catenin信号通路促进肺腺癌进展的机制研究
HSPA4 promotes progression of lung adenocarcinoma by inducing endo-plasmic reticulum stress and activating β-catenin signaling pathway
摘要
Abstract
AIM:This study aims to investigate the role of heat shock protein A4(HSPA4)in promoting the progression of lung adenocarcinoma by inducing endoplasmic reticulum stress(ERS)and activating the Wnt/β-catenin sig-naling pathway,through the detection of its expression in lung adenocarcinoma.METHODS:The expression of HSPA4 in lung adenocarcinoma and its correlation with prognosis were analyzed using the TCGA database.Tissue and blood sam-ples were collected from 60 patients diagnosed with lung adenocarcinoma at The First Affiliated Hospital of Wannan Medi-cal College between January 2020 and December 2023,alongside blood samples from 40 healthy controls.Immunohisto-chemistry,Western blot,and enzyme-linked immunosorbent assay were utilized to detect HSPA4 levels and analyze their relationship with prognosis.In vitro,HSPA4-specific siRNA and pcDNA were employed to knock down or overexpress HS-PA4 in lung adenocarcinoma cells.Cell proliferation was assessed using EdU staining,and the expression levels of HS-PA4,HSPA5,proliferating cell nuclear antigen(PCNA),β-catenin,and its downstream factors,cyclin D1 and c-Myc,were examined.RESULTS:Database analysis revealed significantly elevated expression of HSPA4 in lung adenocarcino-ma patients(P<0.01),which correlated with prognosis(P<0.01).In clinical samples,immunohistochemistry demon-strated significantly higher levels of HSPA4 in cancer tissues compared to adjacent normal tissues(P<0.01).Additional-ly,serum HSPA4 levels were significantly increased in patients compared to controls(P<0.01).In vitro studies using Western blot analysis revealed differential HSPA4 expression across lung adenocarcinoma cell lines,with significantly higher levels observed in A549 and HCC827 cells(P<0.01)and lower levels in H1299 cells(P<0.01).A549 and H1299 cell lines were selected for subsequent experiments.Knockdown of HSPA4 in A549 cells suppressed cell prolifera-tion,downregulated PCNA expression,and reduced the levels of HSPA5,β-catenin,cyclin D1,and c-Myc.Conversely,overexpression of HSPA4 in H1299 cells promoted cell proliferation and PCNA expression while upregulating HSPA5,β-catenin,cyclin D1,and c-Myc.These effects were partially reversed by the endoplasmic reticulum stress(ERS)inhibi-tor 4-PBA.CONCLUSION:HSPA4 promotes lung adenocarcinoma progression by inducing ERS and activating the β-catenin signaling pathway.关键词
肺腺癌/热休克蛋白A4/内质网应激/β-cateninKey words
lung adenocarcinoma/heat shock protein A4/endoplasmic reticulum stress/β-catenin分类
医药卫生引用本文复制引用
秦立龙,王晓彤,汪丽静,臧蕾蕾,程玉生,徐雯..HSPA4诱导内质网应激激活β-catenin信号通路促进肺腺癌进展的机制研究[J].中国病理生理杂志,2026,42(5):875-883,9.基金项目
安徽省卫健委科研重大项目(No.AHWJ2023A10132) （No.AHWJ2023A10132）
