Mechanism of bone sialoprotein(BSP)-mediated promotion of endometrial cancer proliferation and invasion via TGF-β signaling regulation
10.13315/j.cnki.cjcep.2025.11.007
- VernacularTitle:骨唾液酸蛋白BSP调节TGF-β信号通路促进子宫内膜癌增殖和侵袭的机制研究
- Author:
Xiaoling KANG
1
;
Zhenlian LI
;
Huibin LI
;
Dongdong WANG
;
Yuexian LING
;
Jintao FU
;
Yanxia LIAO
;
Yu-juan GUO
;
Zhuzhu HUANG
;
Hongyi GAO
Author Information
1. 广东省妇幼保健院病理科,广州 510442
- Publication Type:Journal Article
- Keywords:
endometrial cancer;
bone sialoprotein;
proliferation;
invasion;
TGF-β
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(11):1446-1453,1461
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the expression of bone sialoprotein(BSP)in the tissues and cells of endome-trial cancer(EC)and its effects on the proliferation and invasion of EC cells.Methods The expression of BSP was assessed by immunohistochemistry in 235 EC tissues and 88 normal endometrial tissues,and its correlation with clinico-pathological features was analyzed.Western blot was used to compare BSP levels between human endometrial carcinoma cell line(HHUA)and normal human endumetial epithelial cells(HEEC).BSP was knocked down in HHUA cells via transient transfection,and the cells were divided into blank control group and BSP-knockdown group.The effects of BSP knockdown on cell cycle,proliferation,migration,invasion,and apoptosis were evaluated using PI staining,CCK-8,scratch,Transwell,and Annexin V-FITC assays,respectively.Protein levels of TGF-β signaling pathway compo-nents were analyzed by Western blot.Results BSP expression was significantly higher in EC tissues than in normal endometrium(P＜0.001)and correlated with lymph node metastasis and advanced FIGO stage(P＜0.05).BSP pro-tein level was also significantly elevated in HHUA cells(2.455 8±0.008 9)compared to HEECs(1.571 2±0.005 4)(P＜0.01).After knockdown,compared with the control group,the proliferation index(74.4±3.33),migration rate(0.48±0.03),and invasion ability(0.36±0.11)of the cells were increased,and the apoptosis rate(25.97％)of the cells was increased(P＜0.05).Furthermore,the expression levels of TGF-β signaling pathway downstream proteins TGF-β1(0.290 4±0.002 3)、TGF-β2(0.292 9±0.001 6)、Smad2(0.469 3±0.001 1)、Smad3(0.247 0±0.001 7)、pAKT(0.382 1±0.001 9)、ATK(0.119 6±0.001 6)and MEK1(0.258 9±0.000 3)in the BSP-knockdown group of EC cells decreased(P＜0.01).Conclusion BSP is highly expressed in endometrial cancer and promotes cancer cell proliferation,invasion,and metastasis by activating the TGF-β signaling pathway.
