肿瘤防治研究2024,Vol.51Issue(4):240-248,9.DOI:10.3971/j.issn.1000-8578.2024.23.1031
慢性饥饿应激通过增强ITGB1表达促进结直肠癌细胞迁移
Chronic Starvation Stress Promotes Migration Ability of Colorectal Cancer Cells by Inducing ITGB1 Upregulation
摘要
Abstract
Objective To investigate the effects of chronic starvation stress on the proliferation and migration of colorectal cancer cells,as well as the underlying mechanisms.Methods By using prolonged serum starvation to simulate chronic starvation stress in tumor cells,we established enduring serum-deprived models of SW480 and DLD-1 cells and observed cellular morphological change.Effects of prolonged serum starvation on SW480 and DLD-1 proliferative and migratory capabilities were assessed using CCK-8 and Transwell assays.Differential gene-expression analysis on SW480 cultured with 1%FBS or 10%FBS medium was followed by GO and KEGG pathway assessments.Migration-related protein interactions were explored using String database and Metascape software,leading to 16 genes being selected for RT-qPCR validation.Protein levels of ITGB1 and key molecules in the relevant pathways were measured.Mobility changes in SW480 were observed through Transwell assay after ITGB1 knockdown or STAT3 inhibition.Results Prolonged serum starvation significantly inhibited the proliferation of SW480 and DLD-1 cells,and DLD-1 mobility,while enhanced SW480 migration.Transcriptome analysis revealed that prolonged serum deprivation caused the upregulation of 3016 genes,among which 283 were involved in cell migration.Metascape analysis identified the correlations among potential core genes ITGB1,CD44,TNS1,STAT3,etc.Prolonged serum deprivation increased the mRNA levels of VTN,TNS1,VEGFA,STAT3,and ITGB1 while also increasing the protein levels of ITGB1 and MMP2 and the phosphorylation levels of JAK2 and STAT3.Mobility reduction in prolonged serum-starved SW480 cells was achieved through ITGB1 knockdown or a STAT3 inhibitor.Conclusion Colorectal cancer cells can endure chronic starvation stress which enhances migration capability by upregulating ITGB1 expression.关键词
饥饿/结直肠瘤/细胞运动/整合素β1/STAT3转录因子Key words
Starvation/Colorectal Cancer/Cell Movement/Integrin beta1/STAT3 Transcription Factor分类
医药卫生引用本文复制引用
李思雨,曹静桦,王凤伟..慢性饥饿应激通过增强ITGB1表达促进结直肠癌细胞迁移[J].肿瘤防治研究,2024,51(4):240-248,9.基金项目
General Program of the National Natural Science Foundation of China(No.81972227) 国家自然科学基金面上项目(81972227) (No.81972227)