SPP1 regulates the proliferation,migration and invasion of colorectal cancer cells through the AKT/GSK3β signaling pathway
10.3781/j.issn.1000-7431.2024.2307-0387
- VernacularTitle:SPP1通过AKT/GSK3β信号通路调控结直肠癌细胞的增殖、迁移与侵袭能力
- Author:
Zhentao HE
1
;
Hao WU
1
;
Defu DAI
1
;
Xueqian SHAO
1
;
Yufeng YUAN
1
;
Zhengpeng YANG
1
Author Information
1. 齐齐哈尔医学院附属第三医院普外科,黑龙江 齐齐哈尔 161000
- Publication Type:Journal Article
- Keywords:
Colorectal cancer;
SPP1;
AKT/GSK3β signaling pathway;
Tumor metastasis
- From:
Tumor
2024;44(4):358-368
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the roles of secretory phosphoprotein 1(SPP1)in the progression of colorectal cancer(CRC)and the underlying mechanism.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to obtain the expression of SPP1 gene in CRC.Immunohistochemistry analysis and Western blotting were used to detect the expression of SPP1 in distal normal colorectal tissues,adjacent tissues,CRC tissues,normal colorectal cell lines and CRC cell lines.The cell viability,colony formation,migration and invasion of CRC cells as well as the activation of AKT/glycogen synthase kinase 3β(GSK3β)signaling pathway and the expression of epithelial-mesenchymal transition(EMT)-related proteins in HT-29 cells and HCT-116 cells were detected by CCK-8 assay,colony formation assay,trranswell assay and Western blotting after SPP1 knockdown in vitro through lentiviral infection carrying shRNA against SPP1 gene.Tumor formation assay was used to detect the effect of SPP1 knockdown on the growth and lung metastasis of transplanted HT-29 tumor in vivo.Results:SPP1 expression was significantly increased in CRC tissues and cell lines(P<0.001)and was associated with poor prognosis of CRC patients according to GEPIA database analysis.The expression of SPP1 protein was significantly upregulated in CRC tissues and cells(P<0.001).After knockdown of SPP1 expression,the cell viability,colony formation,migration and invasion of CRC cells were significantly decreased(P<0.001),the expression of phosphorylated AKT(phospho-AKT,p-AKT),phosphorylated GSK3β(phospho-GSK3β,p-GSK3β),Snail and Vementin were significantly decreased(P<0.001),while E-cadherin expression was significantly increased(P<0.001).Knockdown of SPP1 expression inhibited the growth and lung metastasis of HT-29 cell tumor xenografts in mice.Conclusion:SPP1 knockdown can inhibit the proliferation,migration and invasion of CRC cells,which may be related to the reduction of AKT/GSK3β signaling activity.
