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YAP 和 TAZ 的过表达是结直肠癌预后的独立预测因子，与结肠癌细胞的增殖和转移有关。

Overexpression of YAP and TAZ is an independent predictor of prognosis in colorectal cancer and related to the proliferation and metastasis of colon cancer cells.

机构信息

Department of Oncology, The First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, P. R. China.

出版信息

PLoS One. 2013 Jun 10;8(6):e65539. doi: 10.1371/journal.pone.0065539. Print 2013.

DOI:10.1371/journal.pone.0065539
PMID:23762387
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3677905/
Abstract

BACKGROUND AND OBJECTIVE

Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are nuclear effectors of the Hippo pathway. Although they are abundantly expressed in the cytoplasm and nuclei of human colorectal cancer (CRC), and related to tumor proliferation status, there have been few studies on the predictive role of YAP and TAZ expression on the overall survival of patients with CRC. This study investigated YAP and TAZ expression in both CRC patients and colon cancer cell lines, and assessed their prognostic value.

METHODS

Paraffin-embedded specimens from 168 eligible patients were used to investigate YAP and TAZ expression by immunohistochemistry, and compared with experimental results in colon cancer HCT116 cell line to explore their clinical significance in CRC.

RESULTS

Statistically significant positive correlations were found between protein expression of YAP and TAZ in CRC tissues. Patients with higher YAP or TAZ expression showed a trend of shorter survival times; more importantly, our cohort study indicated that patients with both YAP and TAZ overexpression presented the worst outcomes. This was supported by multivariate analysis. In HCT116 colon cancer cells, the capacity for proliferation, metastasis, and invasion was dramatically reduced by knockdown of YAP and TAZ expressions by siRNA.

CONCLUSIONS

Co-overexpression of YAP and TAZ is an independent predictor of prognosis for patients with CRC, and may account for the higher proliferation, metastasis, and poor survival outcome of these patients.

摘要

背景与目的

Yes 相关蛋白（YAP）和转录共激活因子与 PDZ 结合基序（TAZ）是 Hippo 通路的核效应物。尽管它们在人结直肠癌（CRC）的细胞质和核中大量表达，并且与肿瘤增殖状态有关，但关于 YAP 和 TAZ 表达对 CRC 患者总生存期的预测作用的研究较少。本研究调查了 YAP 和 TAZ 在 CRC 患者和结肠癌细胞系中的表达，并评估了它们的预后价值。

方法

使用免疫组织化学法检测 168 例合格患者的石蜡包埋标本中 YAP 和 TAZ 的表达，并与结肠癌 HCT116 细胞系的实验结果进行比较，以探讨其在 CRC 中的临床意义。

结果

CRC 组织中 YAP 和 TAZ 蛋白表达呈显著正相关。YAP 或 TAZ 表达较高的患者生存时间有缩短趋势；更重要的是，我们的队列研究表明，YAP 和 TAZ 均过表达的患者预后最差。这一结果得到了多变量分析的支持。在 HCT116 结肠癌细胞中，通过 siRNA 下调 YAP 和 TAZ 的表达，细胞的增殖、转移和侵袭能力显著降低。

结论

YAP 和 TAZ 的共过表达是 CRC 患者预后的独立预测因子，可能导致这些患者更高的增殖、转移和不良生存结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/5158dbc13144/pone.0065539.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/bec72603ebd7/pone.0065539.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/3b7d42c0e086/pone.0065539.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/2c697aabe542/pone.0065539.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/07601245f516/pone.0065539.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/5158dbc13144/pone.0065539.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/bec72603ebd7/pone.0065539.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/3b7d42c0e086/pone.0065539.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/2c697aabe542/pone.0065539.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/07601245f516/pone.0065539.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1b1/3677905/5158dbc13144/pone.0065539.g005.jpg

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