更新于：2024-09-19

ECT2

更新于：2024-09-19

基本信息

别名

ARHGEF31、ECT2、epithelial cell transforming 2

+ [2]

简介

Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.

关联

100 项与 ECT2 相关的临床结果

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100 项与 ECT2 相关的转化医学

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0 项与 ECT2 相关的专利（医药）

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370

项与 ECT2 相关的文献（医药）

2024-11-01·Gene

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer

Article

作者: Wu, Xiang-Guang ; Huang, Si-Yuan ; Chen, Jin-Jiao ; Fan, Liang-Sheng ; Zhou, Xiao-Xia ; Wang, Wei ; Ding, Zi-Ang ; Qiu, Yang-Zhi ; Zhong, Xiao-Qing ; Pan, Yu-Hua ; Wu, Yu

OBJECTIVESThe study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection.METHODSDifferentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential.RESULTSUpregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis.CONCLUSIONSECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

2024-09-01·Brain Pathology

The post‐stroke young adult brain has limited capacity to re‐express the gene expression patterns seen during early postnatal brain development

Article

作者: Rupek, Paul ; Capitanescu, Bogdan ; Popa-Wagner, Aurel ; Dandekar, Thomas ; Radu, Eugen ; Ruscu, Mihai ; Hermann, Dirk M

AbstractThe developmental origins of the brain's response to injury can play an important role in recovery after a brain lesion. In this study, we investigated whether the ischemic young adult brain can re‐express brain plasticity genes that were active during early postnatal development. Differentially expressed genes in the cortex of juvenile post‐natal day 3 and the peri‐infarcted cortical areas of young, 3‐month‐old post‐stroke rats were identified using fixed‐effects modeling within an empirical Bayes framework through condition‐specific comparison. To further analyze potential biological processes, upregulated and downregulated genes were assessed for enrichment using GSEA software. The genes showing the highest expression changes were subsequently verified through RT‐PCR. Our findings indicate that the adult brain partially recapitulates the gene expression profile observed in the juvenile brain but fails to upregulate many genes and pathways necessary for brain plasticity. Of the upregulated genes in post‐stroke brains, specific roles have not been assigned to Apobec1, Cenpf, Ect2, Folr2, Glipr1, Myo1f, and Pttg1. New genes that failed to upregulate in the adult post‐stroke brain include Bex4, Cd24, Klhl1/Mrp2, Trim67, and St8sia2. Among the upregulated pathways, the largest change was observed in the KEGG pathway “One carbon pool of folate,” which is necessary for cellular proliferation, followed by the KEGG pathway “Antifolate resistance,” whose genes mainly encode the family of ABC transporters responsible for the efflux of drugs that have entered the brain. We also noted three less‐described downregulated KEGG pathways in experimental models: glycolipid biosynthesis, oxytocin, and cortisol pathways, which could be relevant as therapeutic targets. The limited brain plasticity of the adult brain is illustrated through molecular and histological analysis of the axonal growth factor, KIF4. Collectively, these results strongly suggest that further research is needed to decipher the complex genetic mechanisms that prevent the re‐expression of brain plasticity‐associated genes in the adult brain.

2024-08-13·Proceedings of the National Academy of Sciences

m ⁶ A modification plays an integral role in mRNA stability and translation during pattern-triggered immunity

Article

作者: Luo, Guan-Zheng ; Liu, Chang ; Motley, Jonathan ; Mwimba, Musoki ; Chen, Tianyuan ; He, Chuan ; Greene, George H. ; Xiang, Yezi ; Dong, Xinnian ; Karapetyan, Sargis ; Xu, Guoyong

Plants employ distinct mechanisms to respond to environmental changes. Modification of mRNA by N 6 -methyladenosine (m 6 A), known to affect the fate of mRNA, may be one such mechanism to reprogram mRNA processing and translatability upon stress. However, it is difficult to distinguish a direct role from a pleiotropic effect for this modification due to its prevalence in RNA. Through characterization of the transient knockdown-mutants of m 6 A writer components and mutants of specific m 6 A readers, we demonstrate the essential role that m 6 A plays in basal resistance and pattern-triggered immunity (PTI). A global m 6 A profiling of mock and PTI-induced Arabidopsis plants as well as formaldehyde fixation and cross-linking immunoprecipitation-sequencing of the m 6 A reader, EVOLUTIONARILY CONSERVED C-TERMINAL REGION2 (ECT2) showed that while dynamic changes in m 6 A modification and binding by ECT2 were detected upon PTI induction, most of the m 6 A sites and their association with ECT2 remained static. Interestingly, RNA degradation assay identified a dual role of m 6 A in stabilizing the overall transcriptome while facilitating rapid turnover of immune-induced mRNAs during PTI. Moreover, polysome profiling showed that m 6 A enhances immune-associated translation by binding to the ECT2/3/4 readers. We propose that m 6 A plays a positive role in plant immunity by destabilizing defense mRNAs while enhancing their translation efficiency to create a transient surge in the production of defense proteins.

1

项与 ECT2 相关的新闻（医药）

2023-07-18

·生物制品圈

协和医院：显著抑制细胞增殖和转移，有望成为膀胱癌治疗新靶点

导读：PLAGL2在多种肿瘤中上调，包括膀胱癌(BCa)。然而，PLAGL2在BCa中致瘤作用的机制尚不清楚。近日，北京协和医院团队在国际知名期刊《Cell Death ＆ Disease》上发表题为“PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling”的文章，证明了PLAGL2在BCa组织中过表达并与生存率降低相关。在功能上，PLAGL2缺乏显著抑制BCa细胞体外和体内的增殖和转移。RNA测序、qRT-PCR、免疫印迹、免疫荧光染色、荧光素酶报告基因和ChIP分析显示，过表达的PLAGL2通过反激活RACGAP1破坏Hippo通路，增加YAP1/TAZ活性。进一步的研究表明，PLAGL2通过racgap1介导的RhoA激活激活YAP1/TAZ信号。重要的是，RhoA抑制剂辛伐他汀或YAP1/TAZ抑制剂维替波芬消除了PLAGL2增强的BCa的促增殖和促转移作用。这些发现表明PLAGL2通过RACGAP1/RhoA GTPase/YAP1信号通路促进BCa进展。因此，信号传导的核心节点可能是BCa有希望的治疗靶点。https://www.nature.com/articles/s41419-023-05970-2研究背景 01 膀胱癌(BCa)是泌尿系统最常见的恶性肿瘤之一，2020年全球约有57万新诊断病例和20万死亡病例。近30%的BCa患者在初诊时表现为肌肉侵袭性肿瘤，且已进入晚期。此外，即使采用标准护理(如治愈性手术)，这些患者的五年总生存率也下降了60%。因此，对BCa进展的生物学机制的新见解将提供更好的治疗方式并延长生存期。癌症是一个多步骤的过程，癌变需要许多转录因子(transcription factors, TFs)。失调的tf参与各种癌症的增殖、侵袭和转移等多种促癌事件，包括肝细胞癌(HCC)、结直肠癌(CRC)、胶质瘤和BCa。多形性腺瘤基因样2 (PLAGL2)是PLAGL基因家族的一员，与多种癌症的发生发展密切相关。如Yang等人揭示了PLAGL2在肺腺癌发展中的病理作用。PLAGL2在促进胃肠道癌和CRC进展中的生物学作用也得到了解决。Qu等研究报道PLAGL2表达与BCa预后及淋巴结转移高度相关。然而，PLAGL2在BCa进展中的生物学机制尚不清楚。Hippo通路在进化上是保守的，并调节组织生长和分化。越来越多的证据表明，Hippo通路在癌细胞增殖、凋亡和转移中起着至关重要的作用。在Hippo通路的核心组分中，上游调控因子如MST1/2、SAV1和LATS1/2是肿瘤抑制因子，而下游效应因子如YAP1/TAZ和TEADs是致癌基因。MST1/2激酶及其结合伙伴SAV1磷酸化并激活LATS1/2及其结合伙伴MOB1。激酶模块以抑制肿瘤的方式发挥作用，使YAP1/TAZ的转录模块成员磷酸化并失活，这些转录模块成员保留在细胞质中，随后被蛋白酶体降解。在许多癌症中，Hippo信号被抑制，YAP1和TAZ转运到细胞核中与TEAD家族结合。激活的TEADs可调控CTGF、CYR61等靶基因，这些靶基因不仅参与肿瘤细胞增殖，还参与肿瘤转移。先前的研究已经揭示了失调的tf在Hippo通路中的关键作用。例如，FOXM1的增强通过抑制Hippo信号传导和增加YAP1/TAZ活性来促进宫颈癌细胞的放射抵抗。在胃癌(GC)中，PAX6敲低通过激活Hippo信号通路消除对CDK4/6抑制剂的耐药性。然而，PLAGL2调控Hippo通路的生物学机制尚不清楚。在这项研究中，我们发现PLAGL2是一种通过抑制Hippo信号传导促进BCa进展的致癌基因。PLAGL2在BCa肿瘤组织中过表达，与BCa患者的生存率降低有关。功能研究表明，上调的PLAGL2通过破坏Hippo信号通路激活YAP1/TAZ及其靶基因，从而促进BCa细胞体外和体内的增殖和转移。在机制上，我们发现PLAGL2可激活其下游靶基因RACGAP1，这是Hippo通路的负调控因子。RACGAP1引发ect2介导的RhoA GTPase激活，从而导致YAP1激活。因此，PLAGL2通过调节Hippo信号传导促进BCa进展，表明其作为BCa治疗靶点的潜力。研究结果 02 PLAGL2在BCa中过表达为了探讨PLAGL2在BCa中的作用，我们分析了在线UALCAN网络资源中PLAGL2的表达水平，该资源包含19个邻近正常组织和408个原发肿瘤组织。结果显示，PLAGL2在原发肿瘤组织中显著上调，与肿瘤分期(除了I期肿瘤与正常组织)和组织学类型无关。此外，PLAGL2过表达与无病生存率降低有关(P < 0.005)。PLAGL2在BCa中过表达开发直接针对致癌TF(例如，PLAGL2)的新药物具有挑战性。另外，探索靶向信号轴关键节点的药物可能是一种很有前途的抗癌治疗策略。在本研究中，辛伐他汀和维替波芬通过靶向PLAGL2/RACGAP1/RhoA GTPase/YAP1轴的关键节点，显示出足够的抑制BCa进展的疗效。这两种抑制剂最初并不是为癌症治疗而设计的，但它们强大的抗癌潜力已经在各种癌症中得到了充分的证明，包括前列腺癌、头颈部鳞状细胞癌和乳腺癌。重新定位现有药物不仅可以提供更好的风险与回报权衡，而且有助于提高生产率和降低生产成本。未来的临床研究需要进一步研究辛伐他汀或维替波特芬在BCa中的作用。总之，我们的研究表明，PLAGL2的上调与BCa的不利生存有关，PLAGL2缺乏显著抑制BCa细胞的增殖和转移。此外，PLAGL2抑制Hippo通路，促进YAP1/TAZ的核易位，并通过racgap1介导的RhoA激活增加YAP1/TAZ活性。最后，给予辛伐他汀或维替波芬对BCa的进展有显著的抑制作用。因此，PLAGL2/RACGAP1/RhoA GTPase/YAP1信号是BCa治疗的潜在关键靶点。参考资料：https://www.nature.com/articles/s41419-023-05970-2

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