ID-1靶向NF-κB/SHP2/SMAD/Src通路调控乳腺癌MCF-7细胞进展机制研究OA

Objective To explore the expression and clinical significance of inhibitor of DNA binding 1(ID-1)in breast cancer and its molecular mechanism in human breast cancer MCF-7 cells by targeting the nuclear factor(NF)-κB/Src homology 2 domain-containing protein tyrosine phosphatase(SHP2)/SMAD/Src signaling pathway.Methods The expression of ID-1 in breast cancer tissues and adjacent normal tissues was detected using immunohistochemistry,and its clinical significance was analyzed.Bioinformatics analysis was employed to examine the correlation between ID-1 and key proteins.In the in vivo experiment,45 female mice were selected to establish a breast cancer model and divided into five groups with 9 mice each:Vivo-control group,Vivo-BMP2 group,Vivo-ID-1 mimic+BMP2 group,Vivo-BMP2+PHPS1 group,and Vivo-ID-1 mimic+PHPS1 group.Tumor tissues from each group were dissected,observed,and weighed.Human breast cancer MCF-7 cells were used for in vitro experiments and divided into NC group,BMP2 group,ID-1 mimic+BMP2 group,sulfasalazine+BMP2 group,ID-1 mimic+sulfasalazine+BMP2 group,BMP2+PHPS1 group,and ID-1 mimic+BMP2+PHPS1 group.Protein expression levels were determined by Western blot,and cell migration and cell invasion were evaluated by scratch and Transwell assays,respectively.Results Immunohistochemical result showed that the expression of ID-1 in breast cancer tissues was significantly higher than that in adjacent normal tissues,the difference was statistically significant(P＜0.001).The expression status of ID-1 was closely associated with histological grade,TNM stage,lymph node metastasis,and distant metastasis(P＜0.05).Bioinformatics analysis indicated that ID-1 was correlated with BMP2,NF-κB,SMAD1/8,and Src in breast cancer(P＜0.05).ID-1 promoted the progression of breast cancer tumors in vivo,while inhibition of SHP2 slowed tumor progression(P＜0.05,P＜0.01).Inhibition of SHP2 significantly decreased expression levels of ID-1,NF-κB,phospho(p)-SHP2,p-SMAD1/5/8,and p-Src proteins in vitro(P＜0.05,P＜0.01).Similarly,inhibition of NF-κB reduced expression levels of ID-1,NF-κB,p-SHP2,p-SMAD1/5/8,and p-Src proteins(P＜0.05,P＜0.01).Both ID-1 and BMP2 promoted MCF-7 cell migration,while inhibition of SHP2 or NF-κB significantly reduced cell migration(P＜0.05,P＜0.01).ID-1 and BMP2 also enhanced MCF-7 cell invasion,while inhibition of SHP2 or NF-κB reduced cell invasion(P＜0.05,P＜0.01).Conclusions ID-1 may promote breast cancer invasion and migration by activating the NF-κB/SHP2/SMAD/Src signaling pathway.