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YAP/TAZ促进葡萄糖转运蛋白1（GLUT1）表达并与子宫内膜癌的预后相关。

YAP/TAZ Promote GLUT1 Expression and Are Associated with Prognosis in Endometrial Cancer.

作者信息

Fujita Masayuki, Orisaka Makoto, Mizutani Tetsuya, Fujita Yuko, Onuma Toshimichi, Tsuyoshi Hideaki, Yoshida Yoshio

机构信息

Department of Obstetrics and Gynecology, University of Fukui, Fukui 910-1193, Japan.

Department of Nursing, Faculty of Nursing and Welfare Sciences, Fukui Prefectural University, Fukui 910-1195, Japan.

出版信息

Cancers (Basel). 2025 Aug 1;17(15):2554. doi: 10.3390/cancers17152554.

DOI:10.3390/cancers17152554
PMID:40805250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12345884/
Abstract

: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. : The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. : YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis ( < 0.05). : YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments.

摘要

Yes相关蛋白（YAP）和具有PDZ结合基序的转录共激活因子（TAZ）作为Hippo信号通路中的效应器，因其与肿瘤形成的关联而受到关注。葡萄糖转运蛋白（GLUT）也有助于癌细胞的增殖。在本研究中，我们调查了YAP/TAZ对子宫内膜癌中GLUT1表达的影响，以及YAP/TAZ的临床相关性和预后价值。：使用RT-qPCR评估YAP和TAZ敲低以及YAP过表达对人子宫内膜癌来源的HHUA和Ishikawa细胞中GLUT1表达的影响。此外，我们对100例确诊的子宫内膜癌组织样本进行了免疫组化表达分析。根据染色强度和阳性染色肿瘤细胞的百分比计算免疫反应性评分，范围为0至12。：YAP/TAZ被确定为HHUA和Ishikawa细胞中GLUT1表达调控的重要因素。此外，在子宫内膜癌患者组织中观察到TAZ与GLUT1表达之间存在显著相关性（无进展生存期<0.05），并且TAZ的核表达与不良预后相关（<0.05）。：YAP/TAZ通过GLUT1促进肿瘤生长。因此，对YAP/TAZ进行治疗靶向可能有助于未来治疗方法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/f10053fec8f6/cancers-17-02554-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/e9fafbf832dc/cancers-17-02554-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/e6d1dd1ef81f/cancers-17-02554-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/261a8951dfdf/cancers-17-02554-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/af28d435b01b/cancers-17-02554-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/cd676604eae0/cancers-17-02554-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/ae43e304a898/cancers-17-02554-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/bff00ee14ed8/cancers-17-02554-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/105de51c6ab1/cancers-17-02554-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/f10053fec8f6/cancers-17-02554-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/e9fafbf832dc/cancers-17-02554-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/e6d1dd1ef81f/cancers-17-02554-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/261a8951dfdf/cancers-17-02554-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/af28d435b01b/cancers-17-02554-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/cd676604eae0/cancers-17-02554-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/ae43e304a898/cancers-17-02554-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/bff00ee14ed8/cancers-17-02554-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/105de51c6ab1/cancers-17-02554-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f25/12345884/f10053fec8f6/cancers-17-02554-g009.jpg

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本文引用的文献

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Hypoxia-Regulated Proteins: Expression in Endometrial Cancer and Their Association with Clinicopathologic Features.缺氧调节蛋白：在子宫内膜癌中的表达及其与临床病理特征的关联
Diagnostics (Basel). 2024 Aug 9;14(16):1735. doi: 10.3390/diagnostics14161735.
2
TEAD Inhibition Overcomes YAP1/TAZ-Driven Primary and Acquired Resistance to KRASG12C Inhibitors.TEAD 抑制克服了 YAP1/TAZ 驱动的 KRASG12C 抑制剂的原发性和获得性耐药。
Cancer Res. 2023 Dec 15;83(24):4112-4129. doi: 10.1158/0008-5472.CAN-23-2994.
3
The Hippo pathway in endometrial cancer: a potential therapeutic target?
子宫内膜癌中的河马通路：一个潜在的治疗靶点？
Front Oncol. 2023 Oct 20;13:1273345. doi: 10.3389/fonc.2023.1273345. eCollection 2023.
4
Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy.全基因组 CRISPR 筛选鉴定出多个增强 KRASG12C 抑制剂疗效的合成致死靶点。
Cancer Res. 2023 Dec 15;83(24):4095-4111. doi: 10.1158/0008-5472.CAN-23-2729.
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Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry.采用雌激素受体免疫组化对 NSMP 高危型子宫内膜癌进行预后细化。
Br J Cancer. 2023 Mar;128(7):1360-1368. doi: 10.1038/s41416-023-02141-0. Epub 2023 Jan 23.
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The Hippo signalling pathway and its implications in human health and diseases.Hippo 信号通路及其在人类健康和疾病中的意义。
Signal Transduct Target Ther. 2022 Nov 8;7(1):376. doi: 10.1038/s41392-022-01191-9.
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YAP/TAZ-TEAD is a novel transcriptional regulator of genes encoding steroidogenic enzymes in rat granulosa cells and KGN cells.YAP/TAZ-TEAD 是大鼠颗粒细胞和 KGN 细胞中编码类固醇生成酶的基因的新型转录调节因子。
Mol Cell Endocrinol. 2023 Jan 1;559:111808. doi: 10.1016/j.mce.2022.111808. Epub 2022 Oct 26.
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Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast.抑制 YAP/TAZ-TEAD 活性可诱导人滋养细胞中的滋养细胞分化为合胞滋养细胞。
Mol Hum Reprod. 2022 Sep 29;28(10). doi: 10.1093/molehr/gaac032.
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Hippo-TAZ signaling is the master regulator of the onset of triple-negative basal-like breast cancers. Hippo-TAZ 信号通路是三阴性基底样乳腺癌发生的主调控因子。
Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2123134119. doi: 10.1073/pnas.2123134119. Epub 2022 Jul 11.
10
GLUT1 Immunohistochemistry Is a Highly Sensitive and Relatively Specific Marker for Erythroid Lineage in Benign and Malignant Hematopoietic Tissues.GLUT1 免疫组织化学染色在良、恶性造血组织中是红系分化较敏感和特异的标记物。
Am J Clin Pathol. 2022 Aug 4;158(2):228-234. doi: 10.1093/ajcp/aqac034.