• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

桥粒芯蛋白2通过增强黏着斑和上皮-间质转化促进肺腺癌发展。

Plakophilin-2 Promotes Lung Adenocarcinoma Development via Enhancing Focal Adhesion and Epithelial-Mesenchymal Transition.

作者信息

Wu Yang, Liu Lu, Shen Xiaoyu, Liu Wenjing, Ma Rui

机构信息

Medical Oncology Department of Thoracic Cancer (2), Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning, People's Republic of China.

Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, Liaoning, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Jan 22;13:559-570. doi: 10.2147/CMAR.S281663. eCollection 2021.

DOI:10.2147/CMAR.S281663
PMID:33519235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7837596/
Abstract

BACKGROUND

Lung cancer is one of the most aggressive tumors with high incidence and mortality, which could be classified into lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Overexpression of Plakophilin-2 (PKP2) has been reported in multiple malignancies. However, the expression and function mechanism of PKP2 in LUAD remain illusive.

METHODS

Real-time PCR (RT-PCR) was conducted to assess the expression of PKP2 in LUAD cells and tissues. An integrated analysis of PKP2 expression in The Cancer Genome Atlas (TCGA) was further performed. The effect of PKP2 on cell proliferation and invasion potential were then evaluated with loss-of-function assays in vitro. Xenograft nude mouse models were used to determine the role of PKP2 in LUAD tumorigenicity in vivo. Bioinformatics prediction, immunohistochemistry and Western blot were performed to examine whether PKP2 promoted LUAD development via enhancing focal adhesion and epithelial-mesenchymal transition.

RESULTS

PKP2 expression was highly expressed in LUAD tissues compared with that in normal tissues and predicated poor prognosis of LUAD patients. TCGA LUAD cohort analysis also showed that high expression of PKP2 indicated unfavorable outcomes in LUAD patients. PKP2 expression was also upregulated in lung cancer cells. Functionally, knockdown of PKP2 suppressed lung cancer cell proliferation and invasion in vitro, while inhibited xenograft lung tumor development in vivo. Mechanistically, we demonstrated that high expression of PKP2 in LUAD was correlated with enhanced EMT and focal adhesion. Knockdown of PKP2 inhibited the expression of EMT-related Vimentin and N-cadherin and focal adhesion-associated expression of BMP4, ICAM1, and VCAM1 in xenograft tumors and lung cancer cells.

CONCLUSION

In summary, our findings indicate that PKP2 functions as an oncogene in LUAD, which could be utilized as a novel diagnostic and therapeutic marker for LUAD treatment.

摘要

背景

肺癌是最具侵袭性的肿瘤之一，发病率和死亡率都很高，可分为肺鳞状细胞癌（LUSC）和肺腺癌（LUAD）。已有报道称，在多种恶性肿瘤中存在桥粒芯蛋白2（PKP2）的过表达。然而，PKP2在LUAD中的表达及功能机制仍不清楚。

方法

采用实时荧光定量聚合酶链反应（RT-PCR）检测LUAD细胞和组织中PKP2的表达。进一步对癌症基因组图谱（TCGA）中PKP2的表达进行综合分析。然后通过体外功能缺失实验评估PKP2对细胞增殖和侵袭潜能的影响。利用异种移植裸鼠模型确定PKP2在LUAD体内致瘤性中的作用。进行生物信息学预测、免疫组织化学和蛋白质印迹分析，以检测PKP2是否通过增强黏着斑和上皮-间质转化促进LUAD的发展。

结果

与正常组织相比，PKP2在LUAD组织中高表达，且提示LUAD患者预后不良。TCGA的LUAD队列分析也显示，PKP2的高表达表明LUAD患者预后不佳。PKP2在肺癌细胞中也上调。在功能上，敲低PKP2可抑制体外肺癌细胞的增殖和侵袭，同时抑制体内异种移植肺肿瘤的发展。机制上，我们证明了LUAD中PKP2的高表达与增强的上皮-间质转化和黏着斑相关。敲低PKP2可抑制异种移植肿瘤和肺癌细胞中上皮-间质转化相关的波形蛋白和N-钙黏蛋白的表达以及黏着斑相关的骨形态发生蛋白4、细胞间黏附分子1和血管细胞黏附分子1的表达。

结论

总之，我们的研究结果表明PKP2在LUAD中作为一种癌基因发挥作用，可作为LUAD治疗的一种新的诊断和治疗标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/89e2daf647db/CMAR-13-559-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/16ec91895ecd/CMAR-13-559-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/d94337812269/CMAR-13-559-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/3ad6ce4cf36b/CMAR-13-559-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/b52b12bd6680/CMAR-13-559-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/4d2eff48ea60/CMAR-13-559-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/d1f2b91c5e62/CMAR-13-559-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/89e2daf647db/CMAR-13-559-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/16ec91895ecd/CMAR-13-559-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/d94337812269/CMAR-13-559-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/3ad6ce4cf36b/CMAR-13-559-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/b52b12bd6680/CMAR-13-559-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/4d2eff48ea60/CMAR-13-559-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/d1f2b91c5e62/CMAR-13-559-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa78/7837596/89e2daf647db/CMAR-13-559-g0007.jpg

相似文献

1
Plakophilin-2 Promotes Lung Adenocarcinoma Development via Enhancing Focal Adhesion and Epithelial-Mesenchymal Transition.桥粒芯蛋白2通过增强黏着斑和上皮-间质转化促进肺腺癌发展。
Cancer Manag Res. 2021 Jan 22;13:559-570. doi: 10.2147/CMAR.S281663. eCollection 2021.
2
Plakophilin-2 accelerates cell proliferation and migration through activating EGFR signaling in lung adenocarcinoma.桥粒斑蛋白-2 通过激活肺腺癌中的 EGFR 信号通路加速细胞增殖和迁移。
Pathol Res Pract. 2019 Jul;215(7):152438. doi: 10.1016/j.prp.2019.152438. Epub 2019 May 13.
3
LINC01117 inhibits invasion and migration of lung adenocarcinoma through influencing EMT process.LINC01117 通过影响 EMT 过程抑制肺腺癌的侵袭和迁移。
PLoS One. 2023 Jun 29;18(6):e0287926. doi: 10.1371/journal.pone.0287926. eCollection 2023.
4
High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial-mesenchymal transition in lung adenocarcinoma.角蛋白 6C 的高表达与不良预后相关，并通过调节肺腺癌中的上皮-间充质转化加速癌症增殖和迁移。
Genes Genomics. 2020 Feb;42(2):179-188. doi: 10.1007/s13258-019-00889-5. Epub 2019 Nov 25.
5
SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial-mesenchymal transition (EMT) in lung adenocarcinoma.丝氨酸蛋白酶抑制剂 B5 是一种预后生物标志物，可促进肺腺癌的增殖、转移和上皮间质转化（EMT）。
Thorac Cancer. 2023 Aug;14(23):2275-2287. doi: 10.1111/1759-7714.15013. Epub 2023 Jul 9.
6
LncRNA PCBP1-AS1 correlated with the functional states of cancer cells and inhibited lung adenocarcinoma metastasis by suppressing the EMT progression.长链非编码 RNA PCBP1-AS1 与癌细胞的功能状态相关，并通过抑制 EMT 进展抑制肺腺癌转移。
Carcinogenesis. 2021 Jul 16;42(7):931-939. doi: 10.1093/carcin/bgab047.
7
PAFAH1B3 predicts poor prognosis and promotes progression in lung adenocarcinoma.PAFAH1B3 预测肺腺癌不良预后并促进其进展。
BMC Cancer. 2022 May 9;22(1):525. doi: 10.1186/s12885-022-09617-x.
8
Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis.通过 RT-qPCR、TCGA 和计算机分析分析肺腺癌中 HOXA3 的下调及其相关分子机制。
Int J Oncol. 2018 Oct;53(4):1557-1579. doi: 10.3892/ijo.2018.4508. Epub 2018 Jul 30.
9
NTSR1 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma through the Wnt/β-catenin pathway.NTSR1 通过 Wnt/β-catenin 通路促进肺腺癌的上皮-间质转化和转移。
Mutat Res. 2024 Jul-Dec;829:111877. doi: 10.1016/j.mrfmmm.2024.111877. Epub 2024 Aug 10.
10
Identification of LBX2 as a novel causal gene of lung adenocarcinoma.鉴定 LBX2 为肺腺癌的一个新的致病基因。
Thorac Cancer. 2020 Aug;11(8):2137-2145. doi: 10.1111/1759-7714.13506. Epub 2020 Jun 22.

引用本文的文献

1
Investigation of biomarkers and associated molecular mechanism shared between colorectal cancer and lung adenocarcinoma.结直肠癌和肺腺癌之间共享的生物标志物及相关分子机制的研究。
Discov Oncol. 2025 Aug 12;16(1):1540. doi: 10.1007/s12672-025-03240-5.
2
Low expression of miR-7-5p promotes resistance to radiotherapy in lung cancer through direct upregulation of PKP2 expression.miR-7-5p的低表达通过直接上调PKP2的表达促进肺癌对放疗的抗性。
Sci Rep. 2025 May 15;15(1):16847. doi: 10.1038/s41598-025-01001-6.
3
A novel mitochondrial quality regulation gene signature for anticipating prognosis, TME, and therapeutic response in LUAD by multi-omics analysis and experimental verification.

本文引用的文献

1
Lung Cancer 2020: Epidemiology, Etiology, and Prevention.肺癌 2020：流行病学、病因学和预防。
Clin Chest Med. 2020 Mar;41(1):1-24. doi: 10.1016/j.ccm.2019.10.001.
2
Epidemiology of lung cancer and lung cancer screening programs in China and the United States.中国和美国的肺癌流行病学和肺癌筛查计划。
Cancer Lett. 2020 Jan 1;468:82-87. doi: 10.1016/j.canlet.2019.10.009. Epub 2019 Oct 7.
3
Cancer treatment and survivorship statistics, 2019.2019 年癌症治疗与生存统计
通过多组学分析和实验验证，发现一种用于预测肺腺癌预后、肿瘤微环境和治疗反应的新型线粒体质量调控基因特征。
Cancer Cell Int. 2025 Apr 10;25(1):138. doi: 10.1186/s12935-025-03764-4.
4
Liquid-Liquid Phase Separation in the Prognosis of Lung Adenocarcinoma: An Integrated Analysis.液-液相分离在肺腺癌预后中的综合分析
Curr Cancer Drug Targets. 2025;25(4):323-334. doi: 10.2174/0115680096345676241001081051.
5
Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence.肥胖症中 plakophilin-2 的损伤打破细胞周期动态平衡，导致脂肪细胞衰老。
Nat Commun. 2023 Aug 22;14(1):5106. doi: 10.1038/s41467-023-40596-0.
6
Identification of novel gene signature for lung adenocarcinoma by machine learning to predict immunotherapy and prognosis.基于机器学习的肺腺癌新型基因特征识别，预测免疫治疗和预后。
Front Immunol. 2023 Jul 31;14:1177847. doi: 10.3389/fimmu.2023.1177847. eCollection 2023.
7
Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells.新型人淋巴结衍生基质支持转移性口腔癌细胞的黏附。
BMC Cancer. 2023 Aug 14;23(1):750. doi: 10.1186/s12885-023-11275-6.
8
Endoplasmic reticulum stress-related gene model predicts prognosis and guides therapies in lung adenocarcinoma.内质网应激相关基因模型预测肺腺癌的预后并指导治疗。
BMC Bioinformatics. 2023 Jun 16;24(1):255. doi: 10.1186/s12859-023-05384-z.
9
Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma.基于细胞焦亡的风险评分预测肺腺癌的预后和药物敏感性。
Open Med (Wars). 2023 Mar 13;18(1):20230663. doi: 10.1515/med-2023-0663. eCollection 2023.
10
Identification and validation of novel lung adenocarcinoma subtypes and construction of prognostic models: based on cuprotosis-related genes.基于铜死亡相关基因的肺腺癌新亚型鉴定与验证及预后模型的构建
BMC Pulm Med. 2023 Feb 11;23(1):63. doi: 10.1186/s12890-023-02350-6.
CA Cancer J Clin. 2019 Sep;69(5):363-385. doi: 10.3322/caac.21565. Epub 2019 Jun 11.
4
Plakophilin-2 accelerates cell proliferation and migration through activating EGFR signaling in lung adenocarcinoma.桥粒斑蛋白-2 通过激活肺腺癌中的 EGFR 信号通路加速细胞增殖和迁移。
Pathol Res Pract. 2019 Jul;215(7):152438. doi: 10.1016/j.prp.2019.152438. Epub 2019 May 13.
5
Hyperactivation of ERK by multiple mechanisms is toxic to RTK-RAS mutation-driven lung adenocarcinoma cells.多种机制导致 ERK 的过度激活对 RTK-RAS 突变驱动的肺腺癌细胞具有毒性。
Elife. 2018 Nov 26;7:e33718. doi: 10.7554/eLife.33718.
6
The human PKP2/plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts.人 PKP2/ plakophilin-2 基因在正常和结肠癌相关成纤维细胞中受 Wnt/β-catenin 诱导。
Int J Cancer. 2018 Feb 15;142(4):792-804. doi: 10.1002/ijc.31104. Epub 2017 Oct 31.
7
Up-regulation of plakophilin-2 is correlated with the progression of glioma.桥粒芯蛋白-2的上调与胶质瘤的进展相关。
Neuropathology. 2017 Jun;37(3):207-216. doi: 10.1111/neup.12363. Epub 2017 Jan 26.
8
Smoking correlates with increased cytoskeletal protein-related coding region mutations in the lung and head and neck datasets of the cancer genome atlas.在癌症基因组图谱的肺癌和头颈癌数据集中，吸烟与细胞骨架蛋白相关编码区域突变增加相关。
Physiol Rep. 2016 Dec;4(24). doi: 10.14814/phy2.13045.
9
INTEGRATIVE ANALYSIS FOR LUNG ADENOCARCINOMA PREDICTS MORPHOLOGICAL FEATURES ASSOCIATED WITH GENETIC VARIATIONS.肺癌腺癌的综合分析预测与基因变异相关的形态学特征。
Pac Symp Biocomput. 2017;22:82-93. doi: 10.1142/9789813207813_0009.
10
Knockdown of Plakophilin 2 Downregulates miR-184 Through CpG Hypermethylation and Suppression of the E2F1 Pathway and Leads to Enhanced Adipogenesis In Vitro.桥粒芯蛋白2的敲低通过CpG高甲基化和E2F1途径的抑制下调miR-184，并导致体外脂肪生成增强。
Circ Res. 2016 Sep 2;119(6):731-50. doi: 10.1161/CIRCRESAHA.116.308422. Epub 2016 Jul 28.