PO.TB03.05 · 肿瘤生物学

CTNNA1通过N-cadherin依赖性黏附和RhoA调节促进透明细胞肾细胞癌的侵袭和迁移

CTNNA1 promotes invasion and migration in clear cell renal cell carcinoma via N-cadherin-dependent adhesion and RhoA modulation

编号 3466 展板 5 时间 4/20 02:00–05:00 区域 Section 30 主讲 Shinta Suenaga

分会场 Migration and Invasion

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作者与单位 Authors & Affiliations

Shinta Suenaga, Sei Naito, Hiromi Ito, Yuki Takai, Takafumi Narisawa, Mayu Yagi, Atsushi Yamagishi, Hayato Nishida, Norihiko Tsuchiya

Yamagata University Hospital, Yamagata city, Japan

摘要 Abstract

中文摘要

背景与目的：透明细胞肾细胞癌（ccRCC）常表现出染色体5q31.2的扩增；然而，这一改变的生物学影响仍不明确。位于该区域的CTNNA1调控细胞间黏附，但其在ccRCC中的功能尚未得到充分表征。本研究旨在阐明CTNNA1在ccRCC进展中的作用及其与cadherin介导的黏附和侵袭潜能的关联。方法：分析了在山形大学接受治疗的57例转移性ccRCC病例的全转录组数据，以评估CTNNA1表达及其与5q拷贝数变异的相关性。使用TCGA数据比较cadherin表达谱。使用小干扰RNA（siRNA）对人ccRCC细胞系（A-498、786-O、769-P）进行CTNNA1敲低。通过定量实时PCR（qRT-PCR）和western blot验证表达水平。通过transwell实验测定细胞侵袭和迁移，并通过免疫荧光显微镜检测蛋白定位。结果：CTNNA1表达在具有5q扩增的ccRCC病例中升高，并与侵袭潜能的增加相关。尽管E-cadherin表达低，但CTNNA1与N-cadherin形成复合物并共定位，参与了细胞间黏附。CTNNA1沉默显著降低了侵袭，而过表达则增强了侵袭。免疫荧光显示，在黏附细胞中alphaE-catenin定位于细胞-细胞连接处，而在孤立细胞中则发生核周重分布。RhoA的定位与CTNNA1一致，并在CTNNA1敲低后被破坏，提示其通过RhoA信号参与调控极性和迁移。结论：CTNNA1通过N-cadherin介导的黏附和对RhoA信号调控的调节促进ccRCC细胞侵袭和迁移。CTNNA1可能代表ccRCC转移预防的潜在治疗靶点。

查看英文原文 English abstract

Background and Objectives Clear cell renal cell carcinoma (ccRCC) frequently exhibits amplification of chromosome 5q31.2; however, the biological impact of this alteration remains unclear. CTNNA1, which is located in this region, regulates cell-cell adhesion, but its function in ccRCC has not been fully characterized. This study aimed to clarify the role CTNNA1 in ccRCC progression and its association with cadherin-mediated adhesion and invasive potential. Methods Whole-transcriptome data from 57 metastatic ccRCC cases treated at Yamagata University were analyzed to assess CTNNA1 expression and its correlation with 5q copy number variation. TCGA data were used to compare cadherin expression profiles. Human ccRCC cell lines (A-498, 786-O, 769-P) underwent CTNNA knockdown using small interfering RNA (siRNA). Expression levels were verified by quantitative real-time PCR (qRT-PCR) and western blotting. Cell invasion and migration were measured by trans well assays, and protein localization was examined by immunofluorescence microscopy. Results CTNNA1 expression was elevated in ccRCC cases with 5q amplification and correlated with increased invasive potential. Despite low E-cadherin expression, CTNNA1 formed a complex and co-localized with N-cadherin, contributing to intercellular adhesion. CTNNA1 silencing significantly reduced invasion, while overexpression enhanced it. Immunofluorescence revealed alphaE-catenin localization at cell-cell junctions in adherent cells and a perinuclear redistribution in isolated cells. RhoA localization mirrored CTNNA1 and was disrupted following CTNNA1 knockdown, suggesting its involvement in regulating polarity and migration through RhoA signaling. Conclusions CTNNA1 promotes ccRCC cell invasion and migration through N-cadherin-mediated adhesion and modulation of RhoA signaling regulation. CTNNA1 may represent a potential therapeutic target for metastasis prevention in ccRCC.

利益披露 Disclosure

S. Suenaga, None.. S. Naito, None.. H. Ito, None.. Y. Takai, None.. T. Narisawa, None.. M. Yagi, None.. A. Yamagishi, None.. H. Nishida, None.. N. Tsuchiya, None.

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