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PCDH20 inhibits esophageal squamous cell carcinoma proliferation and migration by suppression of the mitogen-activated protein kinase 9/AKT/β-catenin pathway
Frontiers in Oncology ( IF 3.5 ) Pub Date : 2022-09-28 , DOI: 10.3389/fonc.2022.937716
Yijiao Ning 1 , Chaoqun Deng 1 , Chunhong Li 2 , Weiyan Peng 3 , Chun Yan 3 , Jing Ran 4 , Weihong Chen 3 , Yujia Liu 3 , Jiuyi Xia 3 , Lin Ye 3 , Zhengqiang Wei 1 , Tingxiu Xiang 1
Affiliation  

Aberrant protocadherins (PCDHs) expression trigger tumor invasion and metastasis. PCDH20 anti-tumor functions in various tumor have been identified. Tumor suppression is due to Wnt/β-catenin pathway antagonism and may be suppressed caused by PCDH20 downregulation through promotor methylation, whereas PCDH20 effects and regulation mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. We analyzed PCDH20 effects on ESCC and underlying action mechanisms for PCDH20. We test PCDH20 expression in ESCC tissues and cells by semi-quantitative PCR (RT-PCR) and q-PCR (real-time quantitative polymerase chain reaction). MSP (methylation-specific PCR) was carried out to assess the methylation of PCDH20 in ESCC cells and tissues. Anti-tumor effects of PCDH20 in vitro were assessed by clone formation assay, CCK8 assay, Transwell assay, and flow cytometry. Nude mice tumorigenicity was used to assess PCDH20 anti-tumor effect in vivo. Online database, qPCR, and Western blotting were used to identify the downregulation of MAP3K9 by PCDH20, associated with AKT/β-catenin signaling inactivation. We found that PCDH20 expression was dramatically attenuated in esophageal cancer tissues and cells, maybe due to promotor methylation, and ectopic PCDH20 expression suppressed ESCC malignant biological phenotypes. PCDH20 exerted anti-tumor effects by MAP3K9 downregulation, which suppressed AKT/β-catenin signaling in ESCC cells.

Conclusion

PCDH20 was a tumor suppressor gene, which antagonized AKT/β-catenin signaling pathway in ESCC by decreasing MAP3K9.



中文翻译:

PCDH20通过抑制丝裂原活化蛋白激酶9/AKT/β-catenin通路抑制食管鳞状细胞癌增殖和迁移

异常的原钙粘蛋白 (PCDHs) 表达触发肿瘤侵袭和转移。PCDH20 在各种肿瘤中的抗肿瘤功能已被确定。肿瘤抑制是由于 Wnt/β-catenin 通路的拮抗作用,可能是由 PCDH20 通过启动子甲基化下调引起的,而 PCDH20 在食管鳞状细胞癌 (ESCC) 中的作用和调节机制仍然难以捉摸。我们分析了 PCDH20 对 ESCC 的影响以及 PCDH20 的潜在作用机制。我们通过半定量 PCR (RT-PCR) 和 q-PCR (实时定量聚合酶链反应) 检测 ESCC 组织和细胞中 PCDH20 的表达。进行 MSP(甲基化特异性 PCR)以评估 ESCC 细胞和组织中 PCDH20 的甲基化。PCDH20体外抗肿瘤作用通过克隆形成试验、CCK8试验、Transwell试验、和流式细胞仪。裸鼠致瘤性用于评估 PCDH20 在体内的抗肿瘤作用。在线数据库、qPCR 和蛋白质印迹用于鉴定与 AKT/β-连环蛋白信号失活相关的 PCDH20 对 MAP3K9 的下调。我们发现PCDH20在食管癌组织和细胞中的表达显着减弱,可能是由于启动子甲基化,异位PCDH20表达抑制了ESCC恶性生物学表型。PCDH20 通过 MAP3K9 下调发挥抗肿瘤作用,从而抑制 ESCC 细胞中的 AKT/β-catenin 信号传导。我们发现PCDH20在食管癌组织和细胞中的表达显着减弱,可能是由于启动子甲基化,异位PCDH20表达抑制了ESCC恶性生物学表型。PCDH20 通过 MAP3K9 下调发挥抗肿瘤作用,从而抑制 ESCC 细胞中的 AKT/β-catenin 信号传导。我们发现PCDH20在食管癌组织和细胞中的表达显着减弱,可能是由于启动子甲基化,异位PCDH20表达抑制了ESCC恶性生物学表型。PCDH20 通过 MAP3K9 下调发挥抗肿瘤作用,从而抑制 ESCC 细胞中的 AKT/β-catenin 信号传导。

Conclusion

PCDH20是一种抑癌基因,通过降低MAP3K9来拮抗ESCC中的AKT/β-catenin信号通路。

更新日期:2022-09-28
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