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核内TEAD4与SIX1过表达是I-III期结直肠癌的独立预后标志物。

Nuclear TEAD4 with SIX1 Overexpression is an Independent Prognostic Marker in the Stage I-III Colorectal Cancer.

作者信息

Yu Tong, Song Jinglue, Zhou Hui, Wu Tingyu, Liang Zhonglin, Du Peng, Liu Chen-Ying, Wang Guanghui, Cui Long, Liu Yun

机构信息

Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

Shanghai Colorectal Cancer Research Center, Shanghai, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Feb 17;13:1581-1589. doi: 10.2147/CMAR.S260790. eCollection 2021.

DOI:10.2147/CMAR.S260790
PMID:33628048
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7898202/
Abstract

INTRODUCTION

Stage I-III colorectal cancer patients are under risk of tumor recurrence and metachronous metastasis after radical surgery. An increased expression of transcription factor TEAD4 is associated with epithelial-mesenchymal transition, metastasis and poor prognosis in colorectal cancer. However, the mechanistic role of TEAD4 in driving colon cancer progression and its prognostic value in early stage of CRC remains unclear.

METHODS

In this study, the regulation, function and prognostic significance of TEAD4 and its new direct target gene SIX1 in CRC progression were evaluated using human tissues, molecular and cell biology.

RESULTS

We show that TEAD4 directly upregulates the expression of SIX1 at transcriptional level in CRC cells, establishing that SIX1 is a new direct target gene of TEAD4. TEAD4 promotes EMT and cell migration of CRC cells, while SIX1 knockdown attenuates this effect and SIX1 overexpression enhances this effect, indicating that SIX1 mediates the function of TEAD4 in promoting cell migration in CRC cells. Clinically, nuclear TEAD4, overexpression of SIX1 and nuclear TEAD4 with SIX1 overexpression predict poor prognosis in CRC patients.

DISCUSSION

Our study identifies TEAD4-SIX1-CDH1 form a novel signaling axis, which contributes to CRC progression, and its aberrant expression and activation predicts poor prognostic for CRC patients in stage I-III.

摘要

引言

I-III期结直肠癌患者在根治性手术后有肿瘤复发和异时转移的风险。转录因子TEAD4表达增加与结直肠癌的上皮-间质转化、转移及预后不良相关。然而，TEAD4在驱动结肠癌进展中的机制作用及其在结直肠癌早期的预后价值仍不清楚。

方法

在本研究中，使用人体组织、分子和细胞生物学方法评估TEAD4及其新的直接靶基因SIX1在结直肠癌进展中的调控、功能及预后意义。

结果

我们发现，TEAD4在转录水平直接上调结直肠癌细胞中SIX1的表达，证实SIX1是TEAD4的一个新的直接靶基因。TEAD4促进结直肠癌细胞的上皮-间质转化和细胞迁移，而敲低SIX1可减弱这种作用，过表达SIX1则增强这种作用，表明SIX1介导TEAD4在促进结直肠癌细胞迁移中的功能。临床上，细胞核内的TEAD4、SIX1过表达以及细胞核内TEAD4与SIX1过表达均预示着结直肠癌患者预后不良。

讨论

我们的研究确定TEAD4-SIX1-CDH1形成了一个新的信号轴，该信号轴促进结直肠癌进展，其异常表达和激活预示着I-III期结直肠癌患者预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/f615eb974810/CMAR-13-1581-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/c5d57e948002/CMAR-13-1581-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/13f9be872a2f/CMAR-13-1581-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/1563c3f3f86f/CMAR-13-1581-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/f615eb974810/CMAR-13-1581-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/c5d57e948002/CMAR-13-1581-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/13f9be872a2f/CMAR-13-1581-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/1563c3f3f86f/CMAR-13-1581-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f8/7898202/f615eb974810/CMAR-13-1581-g0004.jpg

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Overexpression of SIX1 is an independent prognostic marker in stage I-III colorectal cancer.
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