更新于：2024-09-19

MACF1

更新于：2024-09-19

基本信息

别名

620 kDa actin-binding protein、ABP620、ACF7

+ [14]

简介

F-actin-binding protein which plays a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules (PubMed:15265687, PubMed:20937854). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane (By similarity). Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics (By similarity). Interaction with CAMSAP3 at the minus ends of non-centrosomal microtubules tethers microtubules minus-ends to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4 (PubMed:15265687). Plays a key role in wound healing and epidermal cell migration (By similarity). Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate microtubule dynamics and polarize hair follicle stem cells (By similarity). As a regulator of actin and microtubule arrangement and stabilization, it plays an essential role in neurite outgrowth, branching and spine formation during brain development (By similarity).

关联

100 项与 MACF1 相关的临床结果

登录后查看更多信息

100 项与 MACF1 相关的转化医学

登录后查看更多信息

0 项与 MACF1 相关的专利（医药）

登录后查看更多信息

198

项与 MACF1 相关的文献（医药）

2024-09-01·International Immunopharmacology

The role of EMG1 in lung adenocarcinoma progression: Implications for prognosis and immune cell infiltration

Article

作者: Wang, Yingying ; Wu, Zhenguo ; Yang, Hui ; Liu, Xiaocen ; Huang, Haoyu ; Lv, Kun ; Wu, Xingwei ; Xie, Zehang

BACKGROUND AND AIMSLung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear.METHODSThe expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter.RESULTSEMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells.CONCLUSIONSEMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.

2024-09-01·Genes & Diseases

MACF1 deficiency suppresses tooth mineralization through IGF1 mediated crosstalk between odontoblasts and ameloblasts

Article

作者: Zhang, Kewen ; Duan, Xiaohong ; Chen, Zhihao ; Lin, Xiao ; Yang, Shaoqing ; Li, Yu ; Qian, Airong ; Qiu, Wuxia ; Miao, Zhiping ; Deng, Xiaoni ; Yang, Chaofei

2024-01-04·Brain

Clinical and genetic characterisation of a large Indian congenital myasthenic syndrome cohort

Article

作者: Lochmüller, Hanns ; Unnikrishnan, Gopikrishnan ; Lorenzoni, Paulo José ; Polavarapu, Kiran ; Preethish-Kumar, Veeramani ; Anjanappa, Ram Murthy ; Porter, Anna ; Bardhan, Mainak ; Horvath, Rita ; Sanka, Sai Bhargava ; Arunachal, Gautham ; Harikrishna, Ganaraja Valakunja ; Keertipriya, Madassu ; Matalonga, Leslie ; Laurie, Steve ; Nashi, Saraswati ; Vengalil, Seena ; Nalini, Atchayaram ; Huddar, Akshata ; Baskar, Dipti ; Sunitha, Balaraju ; Girija, Manu Santhappan ; Padmanabh, Hansashree ; Azuma, Yoshiteru ; Töpf, Ana ; Thompson, Rachel

AbstractCongenital myasthenic syndromes (CMS) are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and β2 adrenergic receptor agonists. In this study, we identified and genetically characterized the largest cohort of CMS patients from India to date.Genetic testing of clinically suspected patients evaluated in a South Indian hospital during the period 2014–19 was carried out by standard diagnostic gene panel testing or using a two-step method that included hotspot screening followed by whole-exome sequencing. In total, 156 genetically diagnosed patients (141 families) were characterized and the mutational spectrum and genotype-phenotype correlation described. Overall, 87 males and 69 females were evaluated, with the age of onset ranging from congenital to fourth decade (mean 6.6 ± 9.8 years). The mean age at diagnosis was 19 ± 12.8 (1–56 years), with a mean diagnostic delay of 12.5 ± 9.9 (0–49 years). Disease-causing variants in 17 CMS-associated genes were identified in 132 families (93.6%), while in nine families (6.4%), variants in genes not associated with CMS were found. Overall, postsynaptic defects were most common (62.4%), followed by glycosylation defects (21.3%), synaptic basal lamina genes (4.3%) and presynaptic defects (2.8%). Other genes found to cause neuromuscular junction defects (DES, TEFM) in our cohort accounted for 2.8%.Among the individual CMS genes, the most commonly affected gene was CHRNE (39.4%), followed by DOK7 (14.4%), DPAGT1 (9.8%), GFPT1 (7.6%), MUSK (6.1%), GMPPB (5.3%) and COLQ (4.5%). We identified 22 recurrent variants in this study, out of which eight were found to be geographically specific to the Indian subcontinent. Apart from the known common CHRNE variants p.E443Kfs*64 (11.4%) and DOK7 p.A378Sfs*30 (9.3%), we identified seven novel recurrent variants specific to this cohort, including DPAGT1 p.T380I and DES c.1023+5G>A, for which founder haplotypes are suspected.This study highlights the geographic differences in the frequencies of various causative CMS genes and underlines the increasing significance of glycosylation genes (DPAGT1, GFPT1 and GMPPB) as a cause of neuromuscular junction defects. Myopathy and muscular dystrophy genes such as GMPPB and DES, presenting as gradually progressive limb girdle CMS, expand the phenotypic spectrum. The novel genes MACF1 and TEFM identified in this cohort add to the expanding list of genes with new mechanisms causing neuromuscular junction defects.

项与 MACF1 相关的新闻（医药）

2023-11-29

·奇点网

敢远处转移？给你腿打折！

*仅供医学专业人士阅读参考以前每当看到病历上“转移性肝细胞癌（HCC）”这几个字，奇点糕都会觉得头皮发麻，还有什么比这更符合雪上加霜的定义呢？原发肿瘤就够难搞了，再叠加上要命的转移，要不是最近几年免疫治疗有所突破，这类患者的预后就实在差到极点了。延缓乃至阻断HCC的远处转移，也是许多科研人员和临床工作者努力的方向。近日，四川大学华西医院唐红、周凌云团队及胡以国团队与西班牙塞维利亚大学团队合作，在Journal of Experimental & Clinical Cancer Research期刊发表了最新研究成果，首次揭示肝癌干细胞（LCSCs）中存在的神经细胞粘附分子（NRCAM）是HCC远处转移的关键[1]。研究显示，NRCAM可以通过细胞骨架分子MACF1介导的β-catenin信号，激活上皮-间质转化（EMT）及远处转移相关的基质金属蛋白酶（MMPs），从而促进LCSCs的迁移和侵袭，并加速其从肿瘤脱落进入血液循环，导致HCC肝内转移和肺转移，对NRCAM及MACF1-β-catenin信号通路进行干预，有望阻断LCSCs相关的HCC远处转移。论文首页截图既往研究已在卵巢癌、结直肠癌等癌种中确认了NRCAM的高表达，并认定它参与了细胞癌变和细胞运动等过程[2]，但还没有在HCC中开展类似分析，而且NRCAM也和MMPs存在可能的瓜葛，它们会不会都是LCSCs远处转移的黑手，必须得查清楚才行。研究团队首先开展了单细胞测序，证实HCC中存在较正常肝脏组织显著更高的NRCAM表达，且TCGA数据库资料也显示，NRCAM高表达HCC患者的生存期显著更短；随后对146例患者肝脏组织样本（其中117例为HCC）的分析也得到了相同结论，且已经发生远处转移的患者组织样本中，NRCAM水平还会更高，甚至周边正常组织中也能检出。进一步数据分析还显示，单独以NRCAM水平作为HCC诊断标志物的准确性，已接近临床最常用的甲胎蛋白（AFP）以及异常凝血酶原（PIVKA-II），三者联合使用时受试者工作特征（ROC）曲线下面积（AUC）为0.91，且NRCAM单独或联合使用，预测HCC远处转移的效能同样尚可（AUC 0.70，联合使用时为0.75），可用于识别早期转移风险高的患者。HCC中存在NRCAM高表达，且与患者预后相关这两步分析一做，NRCAM与HCC远处转移的关系就八九不离十了，研究者们还专门用HCC类器官实验再做了确证，并发现高表达NRCAM的HCC还同时具有干细胞样特征，如WNT/β-catenin信号通路、EMT相关基因的表达水平上升等。接下来，研究团队把目标缩小到LCSCs身上，专门分析NRCAM对这部分“顽敌”的影响：转录组学分析显示，高表达NRCAM的LCSCs往往同时存在MYC基因激活，二者表达水平正相关，且有WNT/β-catenin信号通路和EMT相关基因的高表达，此外还能检测到MMPs中的MMP3/7/14激活，这些关键基因和信号通路的激活大多经由MACF1介导。3D类器官实验则显示，向LCSCs中转染MYC基因并使它们高表达NRCAM后，LCSCs迁移速度就大幅加快；将类器官移植到免疫缺陷小鼠身上后，肿瘤很快就发生了肺转移，足足占据了小鼠肺部的16%，是对照组的10倍还多，说明LCSCs的肺转移能力极强；肝内原发肿瘤也有相似的趋势，占据肝脏的体积是对照组的约5倍。高表达NRCAM且MYC激活的LCSCs类器官肺转移能力极强研究者们将本次研究的意义总结为两方面，一方面是以NRCAM作为血检标志物，用于HCC的确诊和发现远处转移，乃至预测早期HCC患者的远处转移风险，但这还需要更大样本量的前瞻性研究来进一步证实；另一方面就是对NRCAM、MACF1或 β-catenin通路展开治疗性干预，降低LCSCs导致的HCC远处转移风险。参考文献：[1]Zhou L, He L, Liu C H, et al. Liver cancer stem cell dissemination and metastasis: uncovering the role of NRCAM in hepatocellular carcinoma[J]. Journal of Experimental & Clinical Cancer Research, 2023, 42: 311.[2]Conacci-Sorrell M E, Ben-Yedidia T, Shtutman M, et al. Nr-CAM is a target gene of the β-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis[J]. Genes & Development, 2002, 16(16): 2058-2072.本文作者丨谭

临床结果临床研究CSCO会议临床终止