更新于：2024-11-01

NEDD9

更新于：2024-11-01

基本信息

别名

Cas scaffolding protein family member 2、CAS-L、CasL

+ [11]

简介

Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion (PubMed:24574519). As a focal adhesion protein, plays a role in embryonic fibroblast migration (By similarity). May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKL and SHPTP2 to the tyrosine phosphorylated form (PubMed:9020138). Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs (PubMed:17174122). Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse (By similarity). Negatively regulates cilia outgrowth in polarized cysts (By similarity). Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723). Positively regulates RANKL-induced osteoclastogenesis (By similarity). Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory (By similarity).

关联

100 项与 NEDD9 相关的临床结果

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100 项与 NEDD9 相关的转化医学

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0 项与 NEDD9 相关的专利（医药）

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428

项与 NEDD9 相关的文献（医药）

2024-11-01·Neoplasia

NEDD9 is transcriptionally regulated by HDAC4 and promotes breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling pathway

Article

作者: Liu, Wenhong ; Luo, Guanghua

BACKGROUNDBreast cancer is a malignancy with a generally poor prognosis. With the advancement of molecular research, we have gained deeper insights into the cellular processes that drive breast cancer development. However, the precise mechanisms remain elusive.RESULTSBased on the CPTAC database, we found that NEDD9 expression is up-regulated in breast cancer tissues and is associated with poor prognosis in breast cancer patients. Functional experiments showed that NEDD9 promotes tumor growth and metastasis both in vitro and in vivo. Overexpression of NEDD9 disrupts mammary epithelial acinus formation and triggers epithelial-mesenchymal transition in breast cancer cells, effects that are reversed upon NEDD9 gene silencing. Mechanistically, NEDD9 upregulates its expression by inhibiting HDAC4 activity, leading to enhanced H3K9 acetylation of the NEDD9 gene promoter and activation of the FAK/NF-κB signaling pathway. Furthermore, NEDD9 overexpression promotes IL-6 secretion, which further drives breast cancer progression. Notably, NEDD9 activation fosters the pro-tumoral M2 macrophage polarization in the tumor microenvironment. NEDD9 stimulates IL-6 secretion, polarizes monocytes towards an M2-like phenotype, and enhances BC cell invasiveness.CONCLUSIONSThese findings suggest that NEDD9 upregulation plays a pivotal role in breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling axis. Targeting NEDD9 may offer a promising therapeutic approach for breast cancer treatment.

2024-06-01·CHEST Critical Care

Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Antiinflammatory Therapies

Article

作者: Alba, George A ; Haring, Alexis M ; Maron, Bradley A ; Thompson, Taylor ; Alladina, Jehan W ; Giacona, Francesca L ; Hibbert, Kathryn A ; Medoff, Benjamin D ; Schmidt, Eric P

BACKGROUNDThe association of plasma biomarkers and clinical outcomes in ARDS resulting from SARS-CoV-2 infection predate the evidence-based use of immunomodulators.RESEARCH QUESTIONWhich plasma biomarkers are associated with clinical outcomes in patients with ARDS resulting from SARS-CoV-2 infection treated routinely with immunomodulators?STUDY DESIGN AND METHODSWe collected plasma from patients with ARDS resulting from SARS-CoV-2 infection within 24 h of admission to the ICU between December 2020 and March 2021 (N = 69). We associated 16 total biomarkers of inflammation (eg, IL-6), coagulation (eg, D-dimer), epithelial injury (eg, surfactant protein D), and endothelial injury (eg, angiopoietin-2) with the primary outcome of in-hospital mortality and secondary outcome of ventilatory ratio (at baseline and day 3).RESULTSThirty patients (43.5%) died within 60 days. All patients received corticosteroids and 6% also received tocilizumab. Compared with survivors, nonsurvivors demonstrated a higher baseline modified Sequential Organ Failure Assessment score (median, 8.5 [interquartile range (IQR), 7-9] vs 7 [IQR, 5-8]); P = .004), lower Pao₂ to Fio₂ ratio (median, 153 [IQR, 118-182] vs 184 [IQR, 142-247]; P = .04), and higher ventilatory ratio (median, 2.0 [IQR, 1.9-2.3] vs 1.5 [IQR, 1.4-1.9]; P < .001). No difference was found in inflammatory, coagulation, or epithelial biomarkers between groups. Nonsurvivors showed higher median neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) levels (median, 8.4 ng/mL [IQR, 7.0-11.2 ng/mL] vs 6.9 ng/mL [IQR, 5.5-8.0 ng/mL]; P = .0025), von Willebrand factor domain A2 levels (8.7 ng/mL [IQR, 7.9-9.7 ng/mL] vs 6.5 ng/mL [IQR, 5.7-8.7 ng/mL]; P = .007), angiopoietin-2 levels (9.0 ng/mL [IQR, 7.9-14.1 ng/mL] vs 7.0 ng/mL [IQR, 5.6-10.6 ng/mL]; P = .01), and syndecan-1 levels (15.9 ng/mL [IQR, 14.5-17.5 ng/mL] vs 12.6 ng/mL [IQR, 10.5-16.1 ng/mL]; P = .01). Only NEDD9 level met the adjusted threshold for significance (P < .003). Plasma NEDD9 level was associated with 60-day mortality (adjusted OR, 9.7; 95% CI, 1.6-60.4; P = .015). Syndecan-1 level correlated with both baseline (ρ = 0.4; P = .001) and day 3 ventilatory ratio (ρ = 0.5; P < .001).INTERPRETATIONBiomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes in a small cohort of patients with ARDS uniformly treated with immunomodulators. However, endothelial biomarkers, including plasma NEDD9, were associated with 60-day mortality.

2024-05-07·Proceedings of the National Academy of Sciences

Catalysis driven by an amyloid–substrate complex

Article

作者: Sasaki, Daisuke ; Sawazaki, Taka ; Sohma, Youhei

Amine modification through nucleophilic attack of the amine functionality is a very common chemical transformation. Under biorelevant conditions using acidic-to-neutral pH buffer, however, the nucleophilic reaction of alkyl amines (pKa ≈ 10) is not facile due to the generation of ammonium ions lacking nucleophilicity. Here, we disclose a unique molecular transformation system, c atalysis driven by a myloid– s ubstrate comp l ex (CASL), that promotes amine modifications in acidic buffer. Ammonium ions attached to molecules with amyloid-binding capability were activated through deprotonation due to the close proximity to the amyloid catalyst formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH 2 ( NL6 ), derived from islet amyloid polypeptide (IAPP). Under the CASL conditions, alkyl amines underwent various modifications, i.e., acylation, arylation, cyclization, and alkylation, in acidic buffer. Crystallographic analysis and chemical modification studies of the amyloid catalysts suggested that the carbonyl oxygen of the Phe–Gly amide bond of NL6 plays a key role in activating the substrate amine by forming a hydrogen bond. Using CASL, selective conversion of substrates possessing equivalently reactive amine functionalities was achieved in catalytic reactions using amyloids. CASL provides a unique method for applying nucleophilic conversion reactions of amines in diverse fields of chemistry and biology.

项与 NEDD9 相关的新闻（医药）

2023-01-30

·生物谷

STTT：组蛋白去乙酰酶抑制剂通过上调NEDD9的表达促进乳腺癌转移

组蛋白脱乙酰酶(HDACs)对组蛋白赖氨酸残基进行脱乙酰化，重塑染色质，在基因转录中发挥重要作用。组蛋白脱乙酰酶(HDACs)对组蛋白赖氨酸残基进行脱乙酰化，重塑染色质，在基因转录中发挥重要作用。由于在多种癌症亚型中的过度表达和异常活性，HDAC被认为是一个有前景的成功的抗癌药物靶点，并且已经被证明是一个成功的靶点。目前，几种HDAC抑制剂已被FDA批准用于治疗血液系统恶性肿瘤，包括伏立诺(SAHA)、贝力诺(PXD-101)、罗米迪辛(FK-228)和潘诺比坦(LBH589)。然而，HDAC抑制剂在治疗实体瘤方面的成功有限。图片来源：https://doi.org/10.1038/s41392-022-01221-6 近日，来自中国科学院的研究者们在Signal Transduction and Targeted Therapy杂志上发表了题为“Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression”的文章，该研究证明了FAK抑制剂可以逆转通过PAN-HDAC抑制剂上调NEDD9诱导的乳腺癌转移，这可能为乳腺癌提供一种潜在的联合治疗方法。组蛋白脱乙酰酶(HDAC)是一种通过修饰组蛋白来调节基因表达的蛋白水解酶，在肿瘤中常被异常激活。已批准的PAN-HDAC抑制剂已显示出对某些血液系统恶性肿瘤患者的临床益处。在临床试验中，只观察到乳腺癌的治疗成功有限。在这项研究中，研究者宣布针对NEDD9-FAK通路的PAN-HDAC抑制剂在临床前模型中加剧了乳腺癌的转移，这可能严重阻碍其临床成功。NEDD9不是一个癌基因，但最近研究表明，NEDD9在白血病、结肠癌、乳腺癌等多种癌症中都存在高水平或高活性的变化。机制上，PAN-HDAC抑制剂通过抑制HDAC4活性，促进NEDD9基因启动子上的H3K9乙酰化，从而增加NEDD9的表达，进而激活FAK磷酸化。PAN-HDAC抑制剂可以通过增加侵袭性来改变乳腺癌的自然病程，这一认识值得临床关注。此外，尽管NEDD9被报道与乳腺癌的转移有关，但它并没有受到太多的关注，也没有开发出治疗策略。 HDAC4抑制对乳腺肿瘤细胞中NEDD9调控的示意图有助于乳腺转移图片来源：https://doi.org/10.1038/s41392-022-01221-6 综上所述，研究者发现抑制HDAC4激活了NEDD9-FAK信号通路，导致乳腺癌细胞的转移，从而限制了PAN-HDAC抑制剂对乳腺癌的临床疗效。本研究的结果强调了选择性HDAC抑制剂研究和开发的重要性。值得注意的是，FAK抑制剂被发现可以逆转由非特异性HDAC抑制剂诱导的乳腺转移，尽管还需要进一步的证据。（生物谷 Bioon.com）参考文献 Zonglong Hu et al. Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression. Signal Transduct Target Ther. 2023 Jan 6;8(1):11. doi: 10.1038/s41392-022-01221-6.