更新于：2024-11-01

PGAM1

更新于：2024-11-01

基本信息

别名

BPG-dependent PGAM 1、PGAM-B、PGAM1

+ [3]

简介

Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate (PubMed:23653202). Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate (PubMed:23653202).

关联

项与 PGAM1 相关的药物

HK-B99

靶点

PGAM1

作用机制

PGAM1抑制剂

在研机构

复旦大学 [+1]

原研机构

中国药科大学

在研适应症

非小细胞肺癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CN118185914

专利挖掘

靶点

PGAM1

作用机制-

在研机构

华中科技大学同济医学院附属同济医院

原研机构

华中科技大学同济医学院附属同济医院

在研适应症

心血管疾病

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

KH-3 (Allist Pharmaceutical)

靶点

PGAM1

作用机制

PGAM1抑制剂

在研机构-

原研机构

复旦大学

在研适应症-

非在研适应症

胰腺癌

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 PGAM1 相关的临床结果

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100 项与 PGAM1 相关的转化医学

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0 项与 PGAM1 相关的专利（医药）

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384

项与 PGAM1 相关的文献（医药）

2024-10-01·Cancer Biotherapy and Radiopharmaceuticals

Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis

Article

作者: Dong, Caijun ; Yang, Liangwei ; Zhao, Guofang

Background: Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. Materials and Methods: The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. Results: circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. Conclusions: circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.

2024-09-02·Journal of Leukocyte Biology

PGAM1 suppression remodels the tumor microenvironment in triple-negative breast cancer and synergizes with anti–PD-1 immunotherapy

Article

作者: Zhang, Dong ; Ren, Xiubao ; Wang, Wenying ; Sun, Qian ; Yu, Wenwen ; Ma, Shiya ; Wang, Min

AbstractTriple-negative breast cancer is a high-risk form of breast cancer with a high metastatic potential and lack of effective therapies. Immunotherapy has shown encouraging clinical benefits, and its efficacy in triple-negative breast cancer is affected by immunocyte infiltration in the tumor microenvironment. PGAM1 is a key enzyme involved in cancer metabolism; however, its role in the tumor microenvironment remains unclear. In this study, we aimed to investigate the role of PGAM1 in triple-negative breast cancer and determine the potential of PGAM1 inhibition in combination with anti–PD-1 immunotherapy. Our results showed that PGAM1 is highly expressed in triple-negative breast cancer and is associated with poor prognosis. In vivo experiments demonstrated that PGAM1 inhibition synergizes with anti–PD-1 immunotherapy, significantly remodeling the tumor microenvironment and leading to an increase in antitumor immunocytes, such as CD8+ T cells and M1 macrophages, and a reduction in immunosuppressive cell infiltration, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Functional and animal experiments showed that this synergistic mechanism inhibited tumor growth in vitro and in vivo. We identified PGAM1 as a novel target that exhibits an antitumor effect via the regulation of immunocyte infiltration. Our results show that PGAM1 can synergize with anti–PD-1 immunotherapy, providing a novel treatment strategy for triple-negative breast cancer.

2024-09-01·Free Radical Biology and Medicine

G protein pathway suppressor 2 suppresses aerobic glycolysis through RACK1-mediated HIF-1α degradation in breast cancer

Article

作者: Zhang, Liang ; Zhan, Xiangrong ; Liu, Xuewen ; Gu, Manxiang ; Yang, Dan ; Jin, Xin ; Sheng, Songran ; Yu, Qingqing ; Ou, Hongling ; Peng, Wenkang ; Liu, Ying ; Si, Yuan

Aerobic glycolysis has been recognized as a hallmark of human cancer. G protein pathway suppressor 2 (GPS2) is a negative regulator of the G protein-MAPK pathway and a core subunit of the NCoR/SMRT transcriptional co-repressor complex. However, how its biological properties intersect with cellular metabolism in breast cancer (BC) development remains poorly elucidated. Here, we report that GPS2 is low expressed in BC tissues and negatively correlated with poor prognosis. Both in vitro and in vivo studies demonstrate that GPS2 suppresses malignant progression of BC. Moreover, GPS2 suppresses aerobic glycolysis in BC cells. Mechanistically, GPS2 destabilizes HIF-1α to reduce the transcription of its downstream glycolytic regulators (PGK1, PGAM1, ENO1, PKM2, LDHA, PDK1, PDK2, and PDK4), and then suppresses cellular aerobic glycolysis. Notably, receptor for activated C kinase 1 (RACK1) is identified as a key ubiquitin ligase for GPS2 to promote HIF-1α degradation. GPS2 stabilizes the binding of HIF-1α to RACK1 by directly binding to RACK1, resulting in polyubiquitination and instability of HIF-1α. Amino acid residues 70-92 aa of the GPS2 N-terminus bind RACK1. A 23-amino-acid-long GPS2-derived peptide was developed based on this N-terminal region, which promotes the interaction of RACK1 with HIF-1α, downregulates HIF-1α expression and significantly suppresses BC tumorigenesis in vitro and in vivo. In conclusion, our findings indicate that GPS2 decreases the stability of HIF-1α, which in turn suppresses aerobic glycolysis and tumorigenesis in BC, suggesting that targeting HIF-1α degradation and treating with peptides may be a promising approach to treat BC.

项与 PGAM1 相关的新闻（医药）

2023-12-22

·今日头条

新型癌症驱动因子！中山大学发文：肝细胞癌最新进展机制

本文为转化医学网原创，转载请注明出处作者：Rainbow 导读：肝细胞癌（HCC）是导致癌症相关死亡的重要因素，在全球排名第三。近日，中山大学研究团队在期刊《CLINICAL AND TRANSLATIONAL MEDICINE》上在线发表题为“RFX6 facilitates aerobic glycolysis-mediated growth and metastasis of hepatocellular carcinoma through targeting PGAM1”的研究论文，研究表明， RFX6是肿瘤发展的一个重要基因，并揭示了它对肝细胞癌（HCC）进展的影响。研究首次揭示了RFX6对糖酵解的影响，并进一步证明了这种新型RFX6-PGAM1调节轴在HCC进展中的重要性。研究可能为HCC提供一个新的治疗靶点。 https://onlinelibrary.wiley.com/doi/10.1002/ctm2.1511 研究背景 01 肝细胞癌（HCC）是导致癌症相关死亡的重要因素，在全球排名第三。大多数HCC病例被诊断出有多个肿瘤（n>3）、血管侵犯或远处转移，留下了几种治愈的选择。尽管癌症治疗取得了进展，但目前对于HCC的治疗选项有限，有必要理解HCC发展的分子机制并确定特定的新治疗靶点。调节因子X6（RFX6）是一种具有翅膀螺旋转录因子的蛋白，属于高度保守的DNA结合蛋白家族——调节因子X（RFX）家族。RFX6在胰岛中表达，并且对于胰岛细胞分化至关重要。需要进一步详细的研究来阐明其在HCC中的确切作用。磷酸甘油酸变位酶1（PGAM1）是一种重要的糖酵解酶，在本研究中被确定为RFX6的下游靶点之一。最近的研究表明，在包括HCC在内的各种癌症中，PGAM1的异常表达与不良临床结果相关，这暗示了PGAM1在癌症发展中的潜在作用。它还与DNA双链断裂修复有关。除了葡萄糖代谢外，这种糖酵解酶还通过调节肌动蛋白丝的组装加剧了癌细胞的迁移。因此，PGAM1可能主要介导了RFX6在HCC中的促肿瘤功能。在体外和体内过表达RFX6促进了肝细胞癌细胞的增殖和迁移能力 02 为了验证RFX6的生物功能，研究人员选择了Huh7和MHCC-97H细胞构建稳定的RFX6过表达细胞。与对照组相比，RFX6过表达组显示出增强的细胞增殖能力。转移试验显示RFX6过表达增加了HCC细胞的运动能力。在皮下肿瘤模型中，RFX6过表达组的肿瘤体积和重量均大于对照组。在随后构建的同种异体移植模型中，RFX6过表达组显示出比对照组更大的肿瘤负担。肿瘤组织的免疫组织化学染色还显示出RFX6过表达组Ki67阳性细胞数增加。在体内肺转移模型中，RFX6过表达组检测到增加的荧光素信号和转移结节数。这些结果表明，RFX6过表达在体内外均增强了HCC细胞的增殖和运动能力。研究结果 03 综上所述，研究表明， RFX6是肿瘤发展的一个重要基因，并揭示了它对肝细胞癌（HCC）进展的影响。研究首次揭示了RFX6对糖酵解的影响，并进一步证明了这种新型RFX6-PGAM1调节轴在HCC进展中的重要性。研究可能为HCC提供一个新的治疗靶点。参考资料： https://onlinelibrary.wiley.com/doi/10.1002/ctm2.1511 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 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情