Effects of SOX9-activated Wnt/β-catenin signaling pathway on cellular proliferation of esophageal squamous cell carcinoma
10.13315/j.cnki.cjcep.2024.02.009
- VernacularTitle:SOX9活化Wnt/β-catenin信号通路对食管鳞状细胞癌细胞增殖的影响
- Author:
Zhiyu ZHANG
1
;
Lianghai WANG
;
Guixuan XU
;
Feng LI
;
Hong CHEN
Author Information
1. 首都医科大学附属北京朝阳医院病理科,北京 100020
- Keywords:
esophageal neoplasms;
squamous cell carcinoma;
SOX9;
Wnt/β-catenin signaling;
LGK974
- From:
Chinese Journal of Clinical and Experimental Pathology
2024;40(2):158-163,171
- CountryChina
- Language:Chinese
-
Abstract:
Purpose To investigate the effect and molecu-lar mechanism underlying SOX9 during esophageal squamous cell carcinoma(ESCC)cells.Methods Immunohistochemistry(IHC)was used to detect the expression of SOX9 in ESCC tis-sues and adjacent normal tissues.The correlation of SOX9 ex-pression with clinicopathological features and prognosis of ESCC was analyzed.The differentially expressed genes in Eca109-Vec-tor and Eca109-SOX9 cells were detected by Affymetrix miRNA array.qRT-PCR was used to determine the differential gene in TE-1 and TE-1-siSOX9 cells.The relationship between SOX9 and active/unphosphorylated β-catenin levels was detected by Western blot.The effects of Wnt inhibitor LGK974 on the prolif-eration of ESCC cells were detected by CCK-8.Results SOX9 was highly expressed in ESCC(4.58±3.04)as compared with that in adjacent normal tissues(1.56±2.08,P＜0.001).SOX9 was related to histopathological grade and invasion depth(P＜0.05).Kaplan-Meier analysis indicated high SOX9 expres-sion in ESCC was significantly correlated with shorter overall sur-vival(P＜0.05).Transcriptome profiling and qRT-PCR analysis suggested that SOX9 contributed to the regulation of AXIN2,FZD7 and WNT5A.Overexpression of SOX9 in Eca109 cells in-creased active/unphosphorylated β-catenin levels,whereas silen-cing SOX9 caused a decrease.Significant attenuation of cell pro-liferation was observed at various concentrations of LGK974 with-out affecting SOX9 expression on SOX9-expressing cell lines.As expected,this inhibitory effect was not obvious in Eca109-Vector cells when compared with Eca109-SOX9 cells treated with the same concentration of LGK974.Conclusion SOX9 is highly ex-pressed in ESCC and SOX9-mediated Wnt/β-catenin signal path-way activation at least partially contributes to the SOX9-induced ESCC growth.These findings suggest that SOX9 is a promising prognostic marker and therapeutic target for ESCC.
