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YAP1 在结直肠癌中的表达通过其靶基因赋予侵袭表型。

YAP1 expression in colorectal cancer confers the aggressive phenotypes via its target genes.

机构信息

Institute of Gastroenterology of PLA, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

Rocket Force Guangzhou Special Service Center, Guangzhou, China.

出版信息

Cell Cycle. 2024 Jan;23(1):83-91. doi: 10.1080/15384101.2024.2309017. Epub 2024 Jan 23.

Abstract

Yes-associated protein1 (YAP1), a downstream effector of the Hippo pathway, is over-expressed in several types of malignancies. We analyzed retrospectively the TCGA database using 447 colorectal cancer (CRC) samples to determine the correlation between YAP1 expression level and CRC patient prognosis. YAP1-enforced expressed CRC cell lines were constructed using the lentivirus particles containing a YAP1 insert. YAP1 was highly expressed in CRC cancerous tissues and is associated with distant metastasis of CRC patients. Kaplan - Meier analysis indicated that CRC patients with a higher YAP1 expression group ( = 104) had worse disease-free survival (DFS) and overall survival (OS) than lower YAP1 expression group ( = 343) ( = 0.008 and  = 0.022). Univariate and multivariate analysis indicated that the elevated YAP1 expression predicted the aggressive phenotype and was an independent indicator for OS and DFS of CRC patients. YAP1 over-expression in CRC cells enhanced their migration and invasion significantly which can be reversed by AXL, CTGF, or CYR61 interference. The study suggested that YAP1 affected the prognosis of CRC patients and controlled the abilities of invasion and migration of CRC cells via its target genes AXL, CTGF, and CYR61.

摘要

Yes 相关蛋白 1(YAP1)是 Hippo 通路的下游效应物,在多种恶性肿瘤中过表达。我们使用包含 YAP1 插入物的慢病毒颗粒构建了 YAP1 过表达的 CRC 细胞系。YAP1 在 CRC 癌组织中高表达,并与 CRC 患者的远处转移有关。Kaplan-Meier 分析表明,YAP1 表达较高组(=104)的 CRC 患者无病生存率(DFS)和总生存率(OS)比 YAP1 表达较低组(=343)差(=0.008 和=0.022)。单因素和多因素分析表明,YAP1 表达升高预示着侵袭性表型,是 CRC 患者 OS 和 DFS 的独立指标。CRC 细胞中 YAP1 的过表达显著增强了它们的迁移和侵袭能力,而 AXL、CTGF 或 CYR61 的干扰可以逆转这种能力。该研究表明,YAP1 通过其靶基因 AXL、CTGF 和 CYR61 影响 CRC 患者的预后,并控制 CRC 细胞的侵袭和迁移能力。

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