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MPP7通过Wnt/β-连环蛋白信号通路介导上皮-间质转化，促进上皮性卵巢癌细胞极性改变。

MPP7 mediates EMT via Wnt/β-catenin pathway to promote polarity changes in epithelial ovarian cancer cells.

作者信息

Tao Chunlin, Ni Xiaoge

机构信息

Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China.

Department of Obstetrics and Gynecology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.

出版信息

J Cancer. 2024 Jun 17;15(14):4490-4502. doi: 10.7150/jca.96185. eCollection 2024.

DOI:10.7150/jca.96185
PMID:39006077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11242328/
Abstract

Ovarian cancer is one of the gynecological malignancies with the highest mortality rate. Its widespread metastasis is difficult to cure, and the beneficiaries of targeted therapy are still limited, which has been a long-standing bottleneck problem. MAGUK P55 scaffold protein 7 (MPP7) plays an important role in the establishment of epithelial cell polarity, but its potential significance in epithelial ovarian cancer is still unclear. In this study, we investigated the expression profile of MPP7 and its functional role in epithelial ovarian cancer. Through analysis of TCGA and GEO databases, combined with immunohistochemical staining of ovarian tumor tissue chips, it was found that MPP7 is significantly overexpressed in epithelial ovarian cancer tissue, and its high expression is closely related to poor prognosis of patients. It has been verified through cell function experiments that interference with MPP7 can inhibit the proliferation, migration, and invasion of ovarian cancer cells . Performing planar polarity immunofluorescence staining on ovarian cancer cells revealed that interference with MPP7 can cause polarity changes in ovarian cancer cells. The transcriptome sequencing results of the ovarian cancer database were analyzed, and Western Blot was used to verify that MPP7 may mediate EMT via Wnt/β-catenin signaling pathway and promote changes in cell polarity in human epithelial ovarian cancer, thereby promoting cancer progression, demonstrating the potential of MPP7 as a new biomarker and target for the diagnosis and treatment of ovarian cancer.

摘要

卵巢癌是死亡率最高的妇科恶性肿瘤之一。其广泛转移难以治愈，且靶向治疗的受益人群仍然有限，这一直是个长期存在的瓶颈问题。膜相关鸟苷酸激酶P55支架蛋白7（MPP7）在上皮细胞极性建立中起重要作用，但其在卵巢上皮癌中的潜在意义仍不清楚。在本研究中，我们调查了MPP7在上皮性卵巢癌中的表达谱及其功能作用。通过分析TCGA和GEO数据库，并结合卵巢肿瘤组织芯片的免疫组化染色，发现MPP7在上皮性卵巢癌组织中显著过表达，其高表达与患者的不良预后密切相关。通过细胞功能实验证实，干扰MPP7可抑制卵巢癌细胞的增殖、迁移和侵袭。对卵巢癌细胞进行平面极性免疫荧光染色显示，干扰MPP7可导致卵巢癌细胞极性改变。分析卵巢癌数据库的转录组测序结果，并通过蛋白质免疫印迹法验证MPP7可能通过Wnt/β-连环蛋白信号通路介导上皮-间质转化（EMT），并促进人上皮性卵巢癌中细胞极性的改变，从而促进癌症进展，证明了MPP7作为卵巢癌诊断和治疗新生物标志物及靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/71c8589e0a13/jcav15p4490g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/fc88b0d6e500/jcav15p4490g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/b681b8907708/jcav15p4490g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/1270ef98e38c/jcav15p4490g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/71c8589e0a13/jcav15p4490g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/fc88b0d6e500/jcav15p4490g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/b681b8907708/jcav15p4490g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/1270ef98e38c/jcav15p4490g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f8c/11242328/71c8589e0a13/jcav15p4490g004.jpg

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本文引用的文献

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[Cancer incidence and mortality in China, 2022].[2022年中国癌症发病率和死亡率]
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Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.上皮性卵巢癌的蛋白质组学特征分析明确了不同组织学亚型的分子特征和治疗靶点。
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is a potential prognostic marker and is associated with cancer metabolism and immune infiltration in clear cell renal cell carcinoma: a bioinformatics analysis based on the TCGA database.是一种潜在的预后标志物，与透明细胞肾细胞癌的癌症代谢和免疫浸润相关：基于TCGA数据库的生物信息学分析
Transl Androl Urol. 2023 Apr 28;12(4):642-658. doi: 10.21037/tau-23-166.
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MPP7 as a Novel Biomarker of Esophageal Cancer: MPP7 Knockdown Inhibits Esophageal Cancer Cell Migration and Invasion.MPP7作为食管癌的一种新型生物标志物：MPP7基因敲低抑制食管癌细胞的迁移和侵袭。
Life (Basel). 2022 Sep 5;12(9):1381. doi: 10.3390/life12091381.
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UBE2T regulates epithelial-mesenchymal transition through the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer.UBE2T 通过 PI3K-AKT 通路调节上皮-间充质转化，在卵巢癌中发挥致癌作用。
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MPP7 promotes the migration and invasion of breast cancer cells via EGFR/AKT signaling.MPP7 通过 EGFR/AKT 信号促进乳腺癌细胞的迁移和侵袭。
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Not Just Another Scaffolding Protein Family: The Multifaceted MPPs.不只是另一种支架蛋白家族：多面的 MPPs。
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Downregulating SynCAM and MPP6 expression is associated with ovarian cancer progression.下调突触细胞粘附分子（SynCAM）和膜相关蛋白磷酸酶6（MPP6）的表达与卵巢癌进展相关。
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