更新于：2024-05-01

GRB7

growth factor receptor bound protein 7

更新于：2024-05-01

基本信息

别名

B47、Epidermal growth factor receptor GRB-7、GRB7

+ [3]

简介

Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. Promotes activation of down-stream protein kinases, including STAT3, AKT1, MAPK1 and/or MAPK3. Promotes activation of HRAS. Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration. Plays a role in the assembly and stability of RNA stress granules. Binds to the 5'UTR of target mRNA molecules and represses translation of target mRNA species, when not phosphorylated. Phosphorylation impairs RNA binding and promotes stress granule disassembly during recovery after cellular stress (By similarity).

关联

100 项与 GRB7 相关的临床结果

登录后查看更多信息

100 项与 GRB7 相关的转化医学

登录后查看更多信息

0 项与 GRB7 相关的专利（医药）

登录后查看更多信息

320

项与 GRB7 相关的文献（医药）

2023-12-23·Developmental dynamics : an official publication of the American Association of Anatomists

Grb7 knockout mice develop normally but litters born to knockout females fail to thrive.

Review

作者: Kristopher A Lofgren ; Paraic A Kenny

BACKGROUND:

Growth factor receptor-bound 7 (Grb7) is an adaptor protein involved in signal transduction downstream of multiple receptor tyrosine kinases, including ERBB, FGFR, and PDGFR pathways. Experimental studies have implicated Grb7 in regulating cell proliferation, survival, migration, and invasion through its large repertoire of protein-protein interactions.

RESULTS:

Here, we describe the generation and characterization of a Grb7 knockout mouse. These mice are viable and fertile. A lacZ knock-in reporter was used to visualize Grb7 promoter activity patterns in adult tissues, indicating widespread Grb7 expression in glandular epithelium, the central nervous system, and other tissues. The sole defect observed in these animals was a failure of Grb7 knockout females to successfully raise pups to weaning age, a phenotype that was independent of both paternal and pup genotypes.

CONCLUSIONS:

These data suggest a regulatory role for Grb7 in mammary lactational physiology.

2023-12-21·BMC cancer

GRB7 plays a promoting role in the progression of gastric cancer.

Article

作者: Guomin Zhu ; Hu Cai ; Qiang Xiao ; Shukun Zeng ; Xiaohua Jiang ; Donglan Liu

BACKGROUND:

Gastric cancer is a clinically common tumor, showing an upward trend of both incidence and mortality. GRB7 has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of GRB7 in gastric cancer process.

METHODS:

immunohistochemical (IHC) staining using a tissue microarray (TMA), quantitative reverse transcription PCR (qRT-PCR) and Western blotting were performed to detect the expression of genes. Furthermore, gastric cancer cell lines AGS and MGC-803 were transfected with short hairpin RNAs against GRB7. The biological function of GRB7 in gastric cancer cells were examined by CCK-8, flow cytometry, wound healing and Transwell assays. Then, in vivo tumor formation assay was conducted to explore the effects of GRB7 on tumor growth. Finally, expression levels of proteins related to cell functions were determined by Western blotting. Coimmunoprecipitation (CoIP) assay was performed to assess the protein-protein interaction.

RESULTS:

GRB7 was up-regulated in gastric cancer tissues and cell lines, and its expression was inversely proportional to survival of gastric cancer patients. Moreover, GRB7 knockdown inhibited proliferative, migratory abilities, as well as promoted cell apoptosis in gastric cancer cells. Further study suggested that GRB7 silencing could suppress gastric cancer tumor growth in vivo. Furthermore, our study uncovered an important interaction between GRB7 and MyD88. Silencing MyD88 was observed to alleviate the malignant phenotypes promoted by GRB7 in gastric cancer cells.

CONCLUSIONS:

Together, this study provided evidence that GRB7 may be an effective molecular targets for the treatment of gastric cancer.

2023-11-30·Scientific reports

Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways.

Article

作者: Behnaz Saidy ; Richa Vasan ; Rosie Durant ; Megan-Rose Greener ; Adelynn Immanuel ; Andrew R Green ; Emad Rakha ; Ian Ellis ; Graham Ball ; Stewart G Martin ; Sarah J Storr

DARPP-32 is a key regulator of protein-phosphatase-1 (PP-1) and protein kinase A (PKA), with its function dependent upon its phosphorylation state. We previously identified DKK1 and GRB7 as genes with linked expression using Artificial Neural Network (ANN) analysis; here, we determine protein expression in a large cohort of early-stage breast cancer patients. Low levels of DARPP-32 Threonine-34 phosphorylation and DKK1 expression were significantly associated with poor patient prognosis, while low levels of GRB7 expression were linked to better survival outcomes. To gain insight into mechanisms underlying these associations, we analysed the transcriptome of T47D breast cancer cells following DARPP-32 knockdown. We identified 202 differentially expressed transcripts and observed that some overlapped with genes implicated in the ANN analysis, including PTK7, TRAF5, and KLK6, amongst others. Furthermore, we found that treatment of DARPP-32 knockdown cells with 17β-estradiol or PKA inhibitor fragment (6-22) amide led to the differential expression of 193 and 181 transcripts respectively. These results underscore the importance of DARPP-32, a central molecular switch, and its downstream targets, DKK1 and GRB7 in breast cancer. The discovery of common genes identified by a combined patient/cell line transcriptomic approach provides insights into the molecular mechanisms underlying differential breast cancer prognosis and highlights potential targets for therapeutic intervention.

项与 GRB7 相关的新闻（医药）

2024-03-28

·今日头条

显著抑制肿瘤生长并改变微环境！中国医科大学：发现肿瘤特异性免疫治疗靶点

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：研究表明，CCR7作为一种重要的炎症因子，可促进口腔鳞状细胞癌(oral squamous cell carcinoma, OSCC)的增殖和转移，但其在肿瘤微环境(tumor microenvironment, TME)中的作用尚不明确。 3月27日，中国医科大学刘法昱研究团队在期刊《JouRNAl of Experimental & Clinical Cancer Research》发表了研究论文，题为“Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology”。本研究中，研究人员构建了CCR7基因敲除小鼠和OSCC小鼠模型，并通过单细胞RNA测序(scRNA-seq)和生物信息学来分析3只CCR7基因敲除小鼠(KO)和3只野生型小鼠(WT)之间OSCC微环境的差异。使用免疫组化、免疫荧光染色和流式细胞术来分析KO和WT组之间显著不同的细胞类型中关键基因的表达。另外，还进行了体外实验来验证CCR7对M2巨噬细胞极化的影响。研究结果表明，CCR7可促进M2型巨噬细胞极化，从而促进口腔鳞癌细胞的增殖、侵袭和迁移。 https://jeccr-biomedcentral-com.libproxy1.nus.edu.sg/articles/10.1186/s13046-024-03013-y#Sec16 研究背景 01 口腔癌是全球第六大常见恶性肿瘤。超过90%的口腔癌起源于口腔鳞状上皮组织，这种类型的癌症被广泛称为口腔鳞状细胞癌(OSCC)。目前，主要的治疗方案包括手术切除、化疗和放疗，这些治疗方法增加了患者的发病率。尽管这些传统治疗方法取得了进展，但口腔鳞状细胞癌患者的五年生存率仍低于70%。近年来，免疫治疗受到了极大的关注，并在多种恶性肿瘤中取得了良好的效果。尽管抗PD-1/PD-L1抗体已被美国食品药品监督管理局(FDA)批准用于治疗OSCC，但总体缓解率仍然较低。因此，寻找针对OSCC的特异性免疫治疗靶点对患者管理变得越来越重要。研究方法 02 研究人员分析了KO组和WT组因OSCC微环境变化导致的肿瘤生长差异。然后，对WT组(B2、B9、B47)和KO组(B30、B76、B77)的肿瘤进行scRNA-seq。初步质控后共获得70316个细胞。然后，使用Doublet Finder R包排除多细胞的干扰，将无多细胞干扰的58,836个细胞用于后续分析。Seurat R软件包进行数据简化和细胞簇可视化分析，t-SNE软件共显示25个细胞簇。Single R初步的细胞簇可以与部分免疫细胞相匹配，但不能区分成纤维细胞和肿瘤细胞。然后根据报道使用inferCNV R包区分良恶性细胞。最终鉴定出8个簇(1、2、5、6、8、12、14、17)为恶性细胞。另外17个细胞簇被鉴定为良性细胞，然后得到最终的聚类注释结果(见图1h)。图1：CCR7对小鼠口腔鳞状细胞癌微环境的影响——单细胞RNA测序技术分析体外实验中，研究人员将THP-1细胞用PMA诱导为M0型巨噬细胞，再用IL-4 + IL-13诱导为M2型巨噬细胞，实时荧光定量PCR结果显示M2组中M2标志物CD206、ARG-1、IL-10和TGF-β的表达水平高于M0组，表明诱导成功。加入CCR7 mAb后诱导作用明显受到抑制，表明CCR7可阻断M2极化。PCI-4B和PCI-37B细胞与M2型巨噬细胞共培养后，细胞迁移和侵袭能力明显增强，而用CCR7 mAb预处理M2型巨噬细胞后，肿瘤细胞(PCI-4B、PCI-37B)的迁移和侵袭能力明显降低。在划痕实验和CCK-8实验中也观察到类似结果，表明CCR7诱导的M2极化可促进肿瘤细胞的存活、迁移和侵袭。为了研究CCR7的作用机制,研究人员根据SCRA-SEQ的结果,还比较了不同细胞之间的基因变化。研究结论 03 以上结果表明，CCR7基因敲除可显著抑制OSCC的肿瘤生长并影响肿瘤的TME, ScRNA-seq和体外实验结果表明CCR7可能通过抑制Dusp1的表达促进M2型巨噬细胞极化，从而促进OSCC的增殖和转移。参考资料： https://jeccr-biomedcentral-com.libproxy1.nus.edu.sg/articles/10.1186/s13046-024-03013-y#Sec16 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

免疫疗法临床研究