GAPVD1

更新于：2025-05-07

基本信息

别名

DKFZP434C212、GAPex-5、GAPEX5

+ [6]

简介

Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking. In the absence of insulin, it maintains RAB31 in an active state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles. Also involved in EGFR trafficking and degradation, possibly by promoting EGFR ubiquitination and subsequent degradation by the proteasome. Has GEF activity for Rab5 and GAP activity for Ras.

关联

100 项与 GAPVD1 相关的临床结果

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100 项与 GAPVD1 相关的转化医学

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0 项与 GAPVD1 相关的专利（医药）

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项与 GAPVD1 相关的文献（医药）

2025-02-01·Current Cancer Drug Targets

GAPVD1 Promotes the Proliferation of Triple-negative Breast Cancer Cells by Regulating the ERK/MAPK Signaling Pathway

Article

作者: Luo, Pei ; Xia, Zeyu ; Gu, Shanzhi ; Zhang, Lifen ; Wang, Lu ; Ning, Qian ; Zhao, Xinhan ; Shao, Shan ; Luo, Minna

Background:Triple-Negative Breast Cancer (TNBC) accounts for 15–20% of all breast cancers and approximately 50% of breast cancer deaths. Chemotherapy remains the main-stay of systemic treatment due to the lack of effective therapy targets. Thus, more studies are urgently needed to identify new therapeutic targets in TNBC patients.Methods:GAPVD1 expression and prognosis value in breast cancer samples were explored in The Cancer Genome Atlas database (TCGA). GAPVD1 knockdown and overexpression TNBC cell lines were constructed. CCK-8 and colony formation assays were performed to detect cell viability. Flow cytometry analysis was performed to detect cell cycle variation. Western blotting was conducted to determine the levels of target genes. Finally, an enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were per-formed.Results:GAPVD1 is overexpressed in breast cancer tissues and predicts poor prognosis. In vitro experiments demonstrated that GAPVD1 is correlated with cell proliferation and the cell cycle of TNBC cells. Mechanistically, alteration in GAPVD1 expression was found to be associated with cell cycle-related proteins PCNA, Cyclin A, and the activity of the ERK/MAPK signaling pathway. Consistent with these findings, enrichment analysis of GAPVD1-involving partners and signaling pathways revealed that the cellular biosynthetic process, macromolecule biosynthetic process, and cell cycle signaling are related to GAPVD1. In vivo experiment demonstrated that GAPVD1 inhibition impedes tumor growth and expression of cell cycle-related proteins.Conclusion:Taken together, our results indicate that GAPVD1 may participate in TNBC cell growth by regulating the cell cycle and ERK/MAPK signaling pathway.

2024-01-01·DNA and Cell Biology

Screening and Identifying Reference Genes for Erythrocyte Production from Cord Blood CD34+ Cells Exposed to Hypoxia

Article

作者: Lei, Huifen ; Xiao, Jun ; Meng, Fangyuan ; Li, Zhicai ; Li, Cuiying ; Li, Xiaowei

Cord blood (CB) CD34+ cells have the potential to be used to achieve artificial hematopoiesis because of their ability to expand and differentiate in multiple directions. However, the mechanism and molecular changes underlying such differentiation are still unclear. The differentiation of CB CD34+ cells is generally driven by subtle changes in gene expression. A crucial method for examining gene expression is quantitative real-time polymerase chain reaction, but the accuracy of the results is dependent on the use of reliable reference genes. Here, the transcription levels of 10 novel candidate reference genes (EIF4G2, DYNC1H1, LUC7L3, CD46, POLR1D, WSB1, GAPVD1, HGS, LGALS8, and RBM5) and 8 traditional reference genes (GAPDH, YWHAZ, ACTB, B2MG, TBP, HMBS, PPIA, HPRT1) in CB CD34+ cells under different oxygen concentrations were screened and evaluated by using the geNorm and NormFinder algorithms. Comprehensive analysis conducted by RefFinder online tool showed that TBP (a traditional reference gene) and EIF4G2 (a novel reference gene) had the most stable expression, whereas GAPDH and HMBS were the least suitable reference genes under these conditions. These results may serve as a basis for selecting reference genes with stable expression for more accurate normalization under different oxygen concentration stimulation during CB CD34+ cells differentiation.

2024-01-01·International Journal of Biological Sciences

VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk

Article

作者: Ning, Qian ; Liu, Xizhi ; Zhao, Xinhan ; Zhang, Lifen ; Wang, Lu ; Zhao, Lin ; Jing, Xin ; Shao, Shan ; Gu, Shanzhi ; Luo, Minna ; Zhao, Fengyu ; Zhang, Yujiao

Triple-negative breast cancer (TNBC) has long been considered a major clinical challenge due to its aggressive behavior and poor prognosis. Cancer stem cells (CSCs) are known as the main cells responsible for tumor origination, progression, recurrence and metastasis. Here, we report that M2-type tumor-associated macrophages (TAMs) contribute to cancer stemness in TNBC cells via the secretion of VEGFA. Reciprocally, elevated VEGFA expression by TAM-educated TNBC cells acts as a regulator of macrophage polarization, therefore constitute a feed-back loop between TNBC cells and TAMs. Mechanistically, VEGFA facilitates the CSC phenotype via the NRP-1 receptor and downstream GAPVD1/Wnt/β-catenin signaling pathway in TNBC cells. Our study underscores the crosstalk between TNBC cells and TAMs mediated by VEGFA and further clarifies the role and underlying mechanisms of the VEGFA/NRP-1/GAPVD1 axis in regulating cancer stemness. We also document an immunosuppressive function of VEGFA in the tumor microenvironment (TME). Therefore, the present study indicates crosstalk between TNBC cells and TAMs induced by VEGFA and provides a potential implication for the combination of immunotherapy and VEGFA-targeted agents in TNBC therapy.

项与 GAPVD1 相关的新闻（医药）

2024-03-20

·生物谷

西安交通大学研究者们揭示了治疗三阴性乳腺癌的潜在治疗方法

VEGFA在肿瘤细胞和tam之间的相互串扰中起着热点作用。tam衍生的VEGFA可能通过NRP-1/ GAPVD1/Wnt/β-catenin轴以自分泌和旁分泌的方式促进TNBC的癌变。乳腺癌是世界范围内最常见的女性恶性肿瘤。三阴性乳腺癌(triple negative breast cancer, TNBC)是乳腺癌中最具侵袭性的亚型，占乳腺癌的15-20%。巨噬细胞作为肿瘤微环境(tumor microenvironment, TME)的重要组成部分，与肿瘤的发生发展密切相关。在乳腺癌TME中，肿瘤相关巨噬细胞(tumor-associated macrophages, tam)是最丰富的免疫细胞之一。乳腺肿瘤及其免疫环境是相互交织的实体，两者对肿瘤进展都很重要。已有结果表明TNBC中肿瘤细胞与tam之间存在紧密的串扰。然而，TNBC中肿瘤细胞与tam之间相互作用的机制尚不清楚。图片来源：https://pubmed.ncbi.nlm.nih.gov/38169627/ 近日，来自西安交通大学的研究者们在Int J Biol Sci.杂志上发表了题为“VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk”的文章，该研究提示VEGFA诱导的TNBC细胞与tam之间存在串扰，为免疫治疗与VEGFA靶向药物联合治疗TNBC提供了潜在的意义。三阴性乳腺癌(TNBC)由于其侵袭性行为和预后不良一直被认为是一个重大的临床挑战。肿瘤干细胞(Cancer stem cells, CSCs)是肿瘤发生、发展、复发和转移的主要细胞。在这里，研究者报道了m2型肿瘤相关巨噬细胞(tam)通过分泌VEGFA促进TNBC细胞的癌变。反之，经tam教育的TNBC细胞VEGFA表达升高可调节巨噬细胞极化，因此在TNBC细胞和tam之间形成反馈回路。在机制上，VEGFA通过NRP-1受体和下游GAPVD1/Wnt/β-catenin信号通路在TNBC细胞中促进CSC表型。本研究强调了VEGFA介导的TNBC细胞与tam之间的串扰，并进一步阐明了VEGFA/NRP-1/GAPVD1轴在调节肿瘤干细胞中的作用和潜在机制。研究者还记录了VEGFA在肿瘤微环境(TME)中的免疫抑制功能。 VEGFA介导的TAMs与TNBC细胞间的串扰促进乳腺癌干性的示意图图片来源：https://pubmed.ncbi.nlm.nih.gov/38169627/ 综上所述，VEGFA在肿瘤细胞和tam之间的相互串扰中起着热点作用。tam衍生的VEGFA可能通过NRP-1/ GAPVD1/Wnt/β-catenin轴以自分泌和旁分泌的方式促进TNBC的癌变。因此，VEGFA/NRP-1/ GAPVD1轴可能是TNBC治疗的一个有价值的靶点。(生物谷 Bioon.com）参考文献 Lu Wang et al. VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk. Int J Biol Sci. 2024 Jan 1;20(2):446-463. doi: 10.7150/ijbs.86085.

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