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GAB2 and GAB3 are expressed in a tumor stage-, grade- and histotype-dependent manner and are associated with shorter progression-free survival in ovarian cancer.GAB2和GAB3以肿瘤分期、分级和组织学类型依赖的方式表达,并且与卵巢癌较短的无进展生存期相关。
J Cell Commun Signal. 2021 Mar;15(1):57-70. doi: 10.1007/s12079-020-00582-3. Epub 2020 Sep 4.
2
Participation of both Gab1 and Gab2 in the activation of the ERK/MAPK pathway by epidermal growth factor.Gab1和Gab2均参与表皮生长因子对ERK/MAPK通路的激活过程。
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Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated epithelial morphogenesis.Gab1和Gab2在Met受体介导的上皮形态发生中的不同募集与功能
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The absence of Grb2-associated binder 2 (Gab2) does not disrupt NK cell development and functions.Grb2相关结合蛋白2(Gab2)的缺失不会破坏自然杀伤细胞的发育和功能。
J Leukoc Biol. 2004 Oct;76(4):896-903. doi: 10.1189/jlb.0304179. Epub 2004 Jul 7.
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Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression.卵巢癌细胞中GAB2的过表达通过上调趋化因子表达促进肿瘤生长和血管生成。
Oncogene. 2016 Aug 4;35(31):4036-47. doi: 10.1038/onc.2015.472. Epub 2015 Dec 14.
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Synergistic effects of SHP2 and PI3K pathway inhibitors in GAB2-overexpressing ovarian cancer.SHP2和PI3K通路抑制剂在过表达GAB2的卵巢癌中的协同作用。
Am J Cancer Res. 2019 Jan 1;9(1):145-159. eCollection 2019.
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Grb2-associated binding (Gab) proteins in hematopoietic and immune cell biology.造血和免疫细胞生物学中的Grb2相关结合(Gab)蛋白
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Gab2 requires membrane targeting and the Met binding motif to promote lamellipodia, cell scatter, and epithelial morphogenesis downstream from the Met receptor.Gab2需要膜靶向和Met结合基序来促进Met受体下游的片状伪足形成、细胞分散和上皮形态发生。
J Cell Physiol. 2008 Mar;214(3):694-705. doi: 10.1002/jcp.21264.
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Non-redundant roles of the Gab1 and Gab2 scaffolding adapters in VEGF-mediated signalling, migration, and survival of endothelial cells.Gab1和Gab2支架衔接蛋白在内皮细胞VEGF介导的信号传导、迁移及存活中的非冗余作用
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Gab2 is a novel prognostic factor for colorectal cancer patients.Gab2是结直肠癌患者的一种新型预后因素。
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Gab2 plays a carcinogenic role in ovarian cancer by regulating CrkII.Gab2 在卵巢癌中通过调节 CrkII 发挥致癌作用。
J Ovarian Res. 2023 Apr 21;16(1):79. doi: 10.1186/s13048-023-01152-y.
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Identification of a six-gene prognostic signature for bladder cancer associated macrophage.膀胱癌相关巨噬细胞六基因预后特征的鉴定
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Potential Prognostic Biomarkers of OSBPL Family Genes in Patients with Pancreatic Ductal Adenocarcinoma.胰腺导管腺癌患者中OSBPL家族基因的潜在预后生物标志物
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Yay team!: 5.782.太棒了,团队!:5.782。
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Identification of a ceRNA Network in Lung Adenocarcinoma Based on Integration Analysis of Tumor-Associated Macrophage Signature Genes.基于肿瘤相关巨噬细胞特征基因整合分析的肺腺癌ceRNA网络鉴定
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Transcriptomic analysis reveals tumor stage- or grade-dependent expression of miRNAs in serous ovarian cancer.转录组分析揭示了浆液性卵巢癌中 miRNA 与肿瘤分期或分级相关的表达。
Hum Cell. 2021 May;34(3):862-877. doi: 10.1007/s13577-021-00486-3. Epub 2021 Feb 12.

本文引用的文献

1
Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2) in preclinical models of ovarian and uterine cancer.脂质体Grb2反义寡脱氧核苷酸(L-Grb2)在卵巢癌和子宫癌临床前模型中的治疗效果。
Oncotarget. 2020 Jul 21;11(29):2819-2833. doi: 10.18632/oncotarget.27667.
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In silico analysis of DYNLL1 expression in ovarian cancer chemoresistance.卵巢癌化疗耐药中 DYNLL1 表达的计算机分析。
Cell Biol Int. 2020 Aug;44(8):1598-1605. doi: 10.1002/cbin.11352. Epub 2020 Apr 13.
3
MPZL1 promotes tumor cell proliferation and migration via activation of Src kinase in ovarian cancer.MPZL1 通过激活卵巢癌细胞中的Src 激酶促进肿瘤细胞的增殖和迁移。
Oncol Rep. 2019 Aug;42(2):679-687. doi: 10.3892/or.2019.7199. Epub 2019 Jun 12.
4
Gab2 promotes cancer stem cell like properties and metastatic growth of ovarian cancer via downregulation of miR-200c.Gab2 通过下调 miR-200c 促进卵巢癌细胞癌干细胞样特性和转移生长。
Exp Cell Res. 2019 Sep 1;382(1):111462. doi: 10.1016/j.yexcr.2019.06.007. Epub 2019 Jun 10.
5
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.蛋白质组学揭示 NNMT 是癌症相关成纤维细胞的代谢调控大师。
Nature. 2019 May;569(7758):723-728. doi: 10.1038/s41586-019-1173-8. Epub 2019 May 1.
6
Fn14 overcomes cisplatin resistance of high-grade serous ovarian cancer by promoting Mdm2-mediated p53-R248Q ubiquitination and degradation.Fn14 通过促进 Mdm2 介导的 p53-R248Q 泛素化和降解来克服高级别浆液性卵巢癌对顺铂的耐药性。
J Exp Clin Cancer Res. 2019 Apr 25;38(1):176. doi: 10.1186/s13046-019-1171-6.
7
Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer.异质性 CAF-肿瘤球体促进卵巢癌的早期腹膜转移。
J Exp Med. 2019 Mar 4;216(3):688-703. doi: 10.1084/jem.20180765. Epub 2019 Feb 1.
8
Elevated expression of Gab1 promotes breast cancer metastasis by dissociating the PAR complex.Gab1 表达水平升高通过解离 PAR 复合物促进乳腺癌转移。
J Exp Clin Cancer Res. 2019 Jan 21;38(1):27. doi: 10.1186/s13046-019-1025-2.
9
The BioGRID interaction database: 2019 update.生物相互作用数据库(BioGRID):2019 年更新版。
Nucleic Acids Res. 2019 Jan 8;47(D1):D529-D541. doi: 10.1093/nar/gky1079.
10
LncRNA snaR upregulates GRB2-associated binding protein 2 and promotes proliferation of ovarian carcinoma cells.长链非编码 RNA snaR 上调 GRB2 相关结合蛋白 2 并促进卵巢癌细胞增殖。
Biochem Biophys Res Commun. 2018 Sep 10;503(3):2028-2032. doi: 10.1016/j.bbrc.2018.07.152. Epub 2018 Aug 1.

GAB2和GAB3以肿瘤分期、分级和组织学类型依赖的方式表达,并且与卵巢癌较短的无进展生存期相关。

GAB2 and GAB3 are expressed in a tumor stage-, grade- and histotype-dependent manner and are associated with shorter progression-free survival in ovarian cancer.

作者信息

Berkel Caglar, Cacan Ercan

机构信息

Molecular Biology and Genetics Department, Tokat Gaziosmanpasa University, 60250, Tokat, Turkey.

出版信息

J Cell Commun Signal. 2021 Mar;15(1):57-70. doi: 10.1007/s12079-020-00582-3. Epub 2020 Sep 4.

DOI:10.1007/s12079-020-00582-3
PMID:32888136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7904992/
Abstract

Ovarian cancer is the most lethal gynecological malignancy and molecular mechanisms of its progression and metastasis are not completely understood. Some members of GAB (GRB2-associated binding) protein family have been reported to be involved in tumor cell proliferation and metastasis in various cancer types. In the present study, we analyzed the expression of GAB proteins (GAB1, GAB2 and GAB3) in ovarian cancer compared to normal ovarian tissue, in terms of tumor stage, tumor grade and histological type. Differential expression analyses performed in R programming environment using multiple transcriptome datasets (n = 1449) showed that GAB1 expression is decreased in ovarian cancer independently of tumor stage, grade and histotype. Unlike GAB1, expression of GAB2 and GAB3 are increased from early stage to late stage and from low grade to high grade in epithelial ovarian cancer. GAB2 and GAB3 also showed histotype-dependent expression. GAB3 was computed as a top gene whose expression most significantly changed between tumor cells from primary tumor, metastases and ascites. High expression of GAB2 and GAB3 was shown to be associated with shorter progression-free survival in ovarian cancer. This study shows that GAB2 and GAB3 can be important regulators of tumor progression and metastasis in ovarian cancer.

摘要

卵巢癌是最致命的妇科恶性肿瘤,其进展和转移的分子机制尚未完全明确。据报道,GAB(GRB2相关结合)蛋白家族的一些成员参与了多种癌症类型的肿瘤细胞增殖和转移。在本研究中,我们根据肿瘤分期、肿瘤分级和组织学类型,分析了GAB蛋白(GAB1、GAB2和GAB3)在卵巢癌与正常卵巢组织中的表达情况。使用多个转录组数据集(n = 1449)在R编程环境中进行的差异表达分析表明,卵巢癌中GAB1的表达降低,且与肿瘤分期、分级和组织类型无关。与GAB1不同,在上皮性卵巢癌中,GAB2和GAB3的表达从早期到晚期、从低级别到高级别均升高。GAB2和GAB3也表现出组织类型依赖性表达。GAB3被确定为一个顶级基因,其表达在原发性肿瘤、转移灶和腹水中的肿瘤细胞之间变化最为显著。GAB2和GAB3的高表达与卵巢癌患者较短的无进展生存期相关。本研究表明,GAB2和GAB3可能是卵巢癌肿瘤进展和转移的重要调节因子。