肿瘤防治研究2025，Vol.52Issue(7)：562-570,9.DOI:10.3971/j.issn.1000-8578.2025.24.1035
C1q样蛋白4调控乳腺癌干细胞特性的作用机制
Regulatory Mechanism of C1q-Like Protein 4 in Characteristics of Breast Cancer Stem Cells
摘要
Abstract
Objective To investigate the role and underlying mechanism of C1q-like protein 4(C1ql4)in regulating the characteristics of breast cancer stem cells.Methods qRT-PCR was used to detect the expression of C1ql4 in breast cancer and normal breast epithelial cell lines,as well as to verify the transfection efficiency of C1ql4.Western blot analysis was employed to examine the phosphorylation levels of AKT,IKK,and IκB in different groups.An AKT activator was added to MDA-MB-231 cells with C1ql4 knockdown,whereas inhibitors targeting AKT,IKK,IκB,and NF-κB nuclear translocation were separately introduced to C1ql4-overexpressing MCF-7 cells.The nuclear translocation of NF-κB,expression levels of the target genes TNF-α and IL-1β,formation ability of tumorspheres,and proportion of CD44+/CD24-/low stem-like subgroups were analyzed.Results C1ql4 expression in breast cancer cell lines was significantly upregulated compared with that in normal breast epithelial cells.Western blot analysis showed that p-AKT/AKT,p-IKK/IKK,and p-IκB/IκB ratios markedly reduced in C1ql4-knockdown MDA-MB-231 cells(all P<0.05)but significantly increased in C1ql4-overexpressing MCF-7 cells(all P<0.05).Rescue exper-iments demonstrated that the addition of an AKT activator to C1ql4-knockdown MDA-MB-231 cells resulted in the enhanced nuclear translocation of NF-κB,the increased nuclear/cytoplasmic NF-κB ratios,the elevated TNF-α and IL-1β expression levels,and significant recovery of tumorsphere formation ability and the proportion of CD44+/CD24-/low stem-like subpopulations(all P<0.05).Conversely,in C1ql4-overexpressing MCF-7 cells,treatment with AKT,IKK,IκB,or NF-κB nuclear translocation inhibitors led to a reduction in NF-κB nuclear translocation,decreased nuclear/cytoplasmic NF-κB ratios,and declines in TNF-α and IL-1β expression levels,tumorsphere formation ability,and the CD44+/CD24-/low subpopulation(all P<0.05).Conclusion C1ql4 promotes the translocation of NF-κB from the cytoplasm to the nucleus through the PI3K/AKT/NF-κB signaling pathway and enhances the expression of stemness in breast cancer cells.关键词
C1q样蛋白4/乳腺癌/干细胞特性/核转录因子κBKey words
C1q-like protein 4/Breast cancer/Stemness/Nuclear transcription factor κB分类
医药卫生引用本文复制引用
李潇,张圣林,胡潺潺,白璐,徐繁..C1q样蛋白4调控乳腺癌干细胞特性的作用机制[J].肿瘤防治研究,2025,52(7):562-570,9.基金项目
Medical Science Research Project of Hebei Province(No.20240363) 河北省医学科学研究课题计划项目(20240363) （No.20240363）
