预约演示

更新于：2025-05-07

ACSL6

更新于：2025-05-07

基本信息

别名

ACS2、ACSL6、acyl-CoA synthetase long chain family member 6

+ [8]

简介

Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490, PubMed:24269233). Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid.

关联

项与 ACSL6 相关的药物

CN118403167

专利挖掘

靶点

ACSL6

作用机制-

在研机构

中山大学附属第一医院

原研机构

中山大学附属第一医院

在研适应症

肝病

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

100 项与 ACSL6 相关的临床结果

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100 项与 ACSL6 相关的转化医学

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0 项与 ACSL6 相关的专利（医药）

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128

项与 ACSL6 相关的文献（医药）

2025-05-01·Current Medicinal Chemistry

Increased ACSL6 Expression Predicts a Favorable Prognosis in Triple-negative Breast Cancer

Article

作者: Cao, Yueyue ; Qian, Xiaojun ; Diao, Haizhou ; Hua, Hui ; Pan, Shuaikang ; Zhang, Jinguo

Background:Long-chain acyl-coenzyme A synthases (ACSLs) are responsible for the catalysis of fatty acids into their corresponding fatty acyl-CoAs. The dysregulation of ACSLs has been increasingly recognized in cancer patients. However, the function of ACSL6 in triple-negative breast cancer (TNBC) is still completely unknown.Methods:In this study, immunohistochemistry was applied to detect ACSL6 protein expression using a TNBC tissue microarray. Additionally, the mRNA levels of ACSL6 in human normal tissues and pancancer tissues were analyzed using Genotype Tissue Expression (GTEx) datasets and The Cancer Genome Atlas (TCGA) database. The correlations between the levels of ACSL6 expression and clinical characteristics were analyzed. The survival analysis of ACSL6 in TNBC was carried out using the Kaplan‒Meier Plotter online tool. Associations of ACSL6 with immune infiltration analyses were conducted using the ESTIMATE, CIBERSORT, and TISIDB databases. The relationship between ACSL6 and sensitivity to drugs was analyzed from Genomics of Drug Sensitivity in Cancer (GDSC).Results:The results indicated a significant increase in ACSL6 expression in TNBC tissues compared to adjacent normal tissues. However, high ACSL6 expression was significantly associated with favorable survival outcomes in TNBC patients. Enrichment analysis revealed that coexpressed genes of ACSL6 were significantly enriched in various immunity processes. ACSL6 was positively correlated with the infiltration of memory CD4 T cells, while a negative correlation was found between ACSL6 and M2 macrophages and resting dendritic cells. Further analysis revealed that high levels of ACSL6 correlated with increased survival outcomes in cancer patients who received immunotherapy.Conclusion:Altogether, the current findings highlight the potential value of ACSL6 as a diagnostic and prognostic marker in the treatment of TNBC.

2025-04-01·Poultry Science

Transcriptomic analysis of broiler chickens reveals metabolic adaptations to a reduced crude protein diet

Article

作者: Asiamah, Collins Amponsah ; de Las Heras-Saldana, Sara ; Wu, Shu-Biao ; Musigwa, Sosthene ; Kheravii, Sarbast K

Protein is an essential component of poultry diets and directly influences growth performance, profitability, and the environment. While the relationship between animal performance and nutrient intake is modulated by gene expression, the transcriptomic mechanisms underlying broiler adaptation to varying dietary protein levels remain underexplored. This research investigated the liver transcriptomic response of broiler chickens fed a reduced crude protein (RCP) diet, aiming to identify differentially expressed genes (DEGs) and metabolic pathways that may underlie protein metabolism and growth. A total of 256 as-hatched Cobb 500 broilers were fed standard starter and grower diets. At the finisher stage (days 19-28), birds were randomly assigned to one of two treatments: normal crude protein (NCP) or RCP diets, with eight replicates per treatment and 16 birds per replicate. The performance results showed no significant difference in weight gain or feed intake between the groups, but the feed conversion ratio was significantly higher (P < 0.05) in RCP-fed birds. Notably, protein utilization efficiency was significantly higher (P < 0.01) in RCP-fed birds than in NCP-fed birds. Transcriptomic analysis of NCP vs RCP revealed 28 DEGs with 9 upregulated and 19 downregulated, including ACSL6, ME1, IGFBP2, HSD3B1, HAO2, MYO1A, and PNPLA3. Functional enrichment analysis revealed significant involvement of DEGs (P < 0.05) in the PPAR signaling pathway and a tendency toward enrichment in the metabolic pathway (P = 0.053). These findings suggest that metabolic adaptations, supported by the DEGs and increased protein utilization, likely enabled RCP-fed birds to perform comparably to those fed the NCP diet. These insights reveal potential transcriptomic markers for optimizing reduced-protein diets in broiler production, aligning the industry goals of balancing productivity with sustainability.

2025-03-01·Annals of Hematology

Novel ETV6::RAPGEF6 fusion gene in chronic eosinophilic leukemia: compiling evidence on the role of IL3 overexpression in tumorigenesis

Article

作者: Fanjat, Youta ; Deckert, Marcel ; Dadone-Montaudié, Bérengère ; Ferrero, Corinne ; Pichery, Estelle ; Iberti, Mathilde ; Toulon, Pierre ; Loschi, Michael ; Cluzeau, Thomas ; Keslair, Frédérique ; Di Mauro, Ilaria ; Duranton-Tanneur, Valérie

Chronic eosinophilic leukemia (CEL) is a rare myeloproliferative neoplasm. Diagnosis of CEL is often challenging, notably because of the lack of recurrent and specific molecular event. We report here a case of CEL occurring in a 49-year-old man who presented a persistent hypereosinophilia (HE) associated with anemia and thrombopenia. Karyotyping showed a translocation t(5;12)(q31;p13). Targeted RNA Sequencing identified a novel ETV6::RAPGEF6 fusion gene, confirmed by RT-PCR. Despite several lines of treatment, the patient died after 16 months of duration with transformation to acute myeloid leukemia (AML).Contrary to myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), where fusion genes are both class defining and involve tyrosine kinase genes as the 3' partner, fusion genes are exceedingly rare in non-MLN-TK myeloid malignancies with HE. The most reported fusion gene is ETV6::ACSL6, in rare cases. Previously, overexpression of IL3 (interleukin 3) has been described in myeloid neoplasms with ETV6::ACSL6 (previously named ACS2). In our case of CEL with the ETV6::RAPGEF6 fusion, we also demonstrated overexpression of IL3, which could potentially result from the proximity of the IL3 gene to RAPGEF6, similar to what is observed with ACSL6 and IL3. The use of RNA sequencing in routine diagnosis of CEL could provide evidence for clonal event such as gene fusion, improving diagnosis as well as prognosis and therapeutic approaches.

项与 ACSL6 相关的新闻（医药）

2024-09-27

·奇点网

一对促癌CP诞生了！

*仅供医学专业人士阅读参考IL-18最初以一种“正面”的形象出现在我们的视野中，这是因为它可以增强T细胞和NK细胞的免疫功能。然而近年来，不断有研究显示，IL-18似乎没有表面看起来那么正派，它也可以通过激活NF-κB通路，来促进肿瘤进展和免疫逃逸。只不过，这背后的机制，我们还不得而知。近期，中山大学附属第一医院王子洋/何伟玲团队、珠海市人民医院陆骊工团队、广州大学王雄军团队联合发表了一篇研究，他们发现，长链酰基辅酶A合成酶6（ACSL6）是IL-18介导肝癌进展和免疫逃逸的关键因子。具体来说，他们发现，IL-18会使ACSL6 S674点位磷酸化（ACSL6 pS674）和细胞膜异位。而ACSL6 pS674可通过促进IL-18受体（IL18R1-IL18RAP）异二聚体的稳定形成，激活了IL-18R1/NF-κB信号通路，进一步上调了多种促癌基因的表达，最终促进了肝癌的生长和转移。此外，研究还发现，ACSL6 pS674还可以通过招募肿瘤相关的中性粒细胞（TANs）和巨噬细胞（TAMs），来抑制肿瘤浸润性CD8阳性T细胞的活性，进而导致肿瘤免疫逃逸。而抑制ACSL6的磷酸化则可以改善这一现象，并增强抗PD-1抗体的治疗效果。这一看，IL-18就像一个敌特，需要跟ACSL6这个接头的合作，才能完成偷摸给癌细胞传递消息（NF-κB通路）的任务啊。研究发表在《科学·进展》上[1]。论文首页截图既往有研究显示，参与脂肪酸分解和合成的关键酶，ACSL，其表达上调与包括肝癌在内的多种癌症有关。而上文也提到，IL-18能介导肿瘤进展和免疫逃逸。基于此，研究人员想知道，在肝癌进展和免疫逃逸过程中，IL-18和ACSL之间是否存在某种关联。鉴于ACSL家族成员众多，研究人员先是利用基因表达数据库分析了多种ACSL在肝癌组织和相邻正常肝组织中的表达情况，结果发现，ACSL6在肝癌组织中的表达水平明显上调，且与患者的不良预后相关。ACSL6在肝癌组织中表达上调随后的体外研究显示，敲除ACSL6能明显抑制肝癌细胞的增殖和迁移，反之，过表达ACSL6则会促进肝癌细胞的增殖和迁移。更重要的是，ACSL6的促癌作用与其代谢酶活性无关（过表达酶活性丧失突变型ACSL6能恢复ACSL6敲除对肝癌细胞增殖和迁移的抑制作用）。同样，研究人员也在小鼠体内也观察到了以上现象。体外实验接下来，研究人员探究了ACSL6促进肝癌进展的机制。利用质谱分析，研究人员在5种与ACSL6相互作用的蛋白质中发现，IL-18R1与ACSL6之间的相互作用最强。随后的免疫共沉实验显示，IL-18R1与ACSL6之间的相互作用发生在细胞膜上。IL-18R1与ACSL6之间的相互作用进一步，机制上，通过磷酸化位点突变、激酶抑制剂与肝癌细胞共培养等一系列实验，研究人员发现，IL-18可激活激酶ERK2，并诱导ACSL6在S674位点发生磷酸化。ACSL6 pS674随后易位至细胞膜，在那里与IL-18R1结合，并促进IL18R1-IL18RAP异二聚体的稳定形成，实现了IL-18/IL-18R1/NF-κB信号通路的传导，进一步上调了多种促癌基因（如与肿瘤生长迁移有关基因GADD45B和MMP3）的表达，最终促进了肝癌的生长和转移。研究机制图研究还发现，ACSL6 pS674可以通过激活IL-18R1/NF-κB信号通路，上调趋化因子CXCL1和CXCL5的表达，并促进TANs和TAMs的招募，来抑制肿瘤浸润性CD8阳性T细胞的活性，进而导致肿瘤免疫逃逸。最后，通过抑制ACSL6磷酸化，研究人员发现，无论是敲除ACSL6还是对ACSL6的S674位点进行突变（rAcsl6 S674A），均可以增强抗PD-1抗体的疗效，表现为肿瘤浸润的CD8阳性T细胞数量的增加，以及TANs和TAMs数量的减少。此外，临床样本分析也发现，ACSL6 pS674水平与NF-κB信号和CXCL1表达正相关，与患者预后负相关。总之，该研究揭示了IL-18是靠与ACSL6合作，来实现NF-κB信号通路的传导，进而促进了肝癌进展和免疫逃逸。这一结果也为未来肝癌的治疗提供了新的思路。------奇点糕近期推出了《2024ASCO年会深度盘点》课程，为大家系统盘点了2024ASCO年会上实体瘤领域的重磅进展，让您在100分钟内迅速深入把握前沿。长按识别下图中的二维码即可购买，购买后您可以在「奇点网小程序」收听，或下载奇点网「医学奇点」苹果客户端收听。如果遇到任何技术问题，大家可以戳我们下图中的客服小伙伴来解决~~参考文献：[1]Di Y,Wang Z,Xiao J,Zhang X,Ye L,Wen X,Qin J,Lu L,Wang X,He W.ACSL6-activated IL-18R1-NF-κB promotes IL-18-mediated tumor immune evasion and tumor progression.Sci Adv.2024 Sep 20;10(38):eadp0719.本文作者丨张金旭

细胞疗法免疫疗法引进/卖出

2024-02-21

·奇点网

反油酸抗癌有什么说头？

*仅供医学专业人士阅读参考前不久，我们分享过华中科技大学的一项研究成果，研究团队揭示低密度脂蛋白（LDL）竟为抗肿瘤免疫出一份力[1]。这次，华中科技大学的另一组研究团队表明，让心血管避之不及的又一号危险角色——反油酸，也能在癌症免疫治疗中找到一份合适工作[2]。华中科技大学同济医学院的王维民、吕付佳与附属同济医院的褚倩等人发现，参与脂质代谢的酶ACSL5是肿瘤抑制因子，通过加强肿瘤细胞的抗原呈递来促进T细胞介导的抗肿瘤效应。在饮食中添加ASCL5的催化底物反油酸，可以抑制肿瘤进展并增强PD-1抑制剂治疗的敏感性。论文于近日发表在《细胞·代谢》期刊上。论文首页截图长链脂肪酸是细胞的重要能量来源和细胞膜组成成分，参与调节许多生物学过程，属于中立资源，为免疫细胞和肿瘤细胞等各种类型细胞所利用。再加上长链脂肪酸在各个细胞中的代谢方式有所不同，类型众多的长链脂肪酸究竟是敌是友，以及如何将其利用起来化解肿瘤危机，是科学家们长久以来探讨的课题。对于细胞来说，要想将长链脂肪酸化为己用，需要由酰基辅酶A合成酶长链家族（ACSLs）插手。ACSL催化长链脂肪酸与辅酶A结合，从而将长链脂肪酸转化为可供细胞代谢利用的形式，进一步参与脂肪酸的氧化代谢、合成脂类等生物学过程。ACSL家族包括ACSL1、ACSL3、ACSL4、ACSL5、ACSL6，具有不同的底物偏好。在这项研究中，研究团队发现，在多种组织类型中广泛表达的ACSL5是个肿瘤抑制因子。ACSL5在肿瘤细胞中的过表达显著抑制肿瘤生长，表达缺陷导致肿瘤加速生长。更重要的是，ACSL5高水平表达与黑色素瘤患者、肺腺癌患者总体生存率改善相关。与不表达相比，特异性表达ACSL5的肿瘤生长受抑制顺着这条线索查下去，研究团队揭示ACSL5如何协助T细胞对抗肿瘤。结合遗传学手段和小鼠实验，他们发现，ASCL5能够通过调节转录因子NLRC5的表达，进而促进肿瘤细胞表达主要组织相容性复合体I类（MHC-I）、增强MHC-I介导的抗原呈递，从而增强细胞毒性T细胞介导的免疫应答。ASCL6缺陷会损害MHC-I的表达，并减弱PD-1抑制剂对荷瘤小鼠的疗效。机制图进一步研究表明，反油酸作为ASCL5的特异性催化底物，饮食中添加反油酸便可以有效增强黑色素瘤小鼠的肿瘤细胞抗原提呈能力，使肿瘤细胞对T细胞介导的免疫杀伤更加敏感。不仅如此，补充反油酸还与PD-1抑制剂具有协同作用，增强其疗效。肺腺癌对于免疫检查点抑制剂疗法通常具有耐药性，PD-1抑制剂无法有效抑制荷瘤小鼠的肿瘤进展；而研究团队通过饮食补充反油酸后，发现接受PD-1抑制剂治疗的荷瘤小鼠肿瘤生长得到了更好的控制，存活率显著提高，对体重没有明显影响。研究团队还利用患者队列评估研究结论在免疫治疗中的临床意义。结果显示，与无反应者相比，对PD-1抑制剂有反应的肺腺癌患者在治疗基线时的反油酸血浆水平更高，并且高水平的反油酸与患者更好的总生存期或无进展生存期相关，表明反油酸血浆水平可作为临床上免疫治疗反应的预测因子。饮食补充反油酸与免疫治疗有协同作用（G-I）；反油酸可作为免疫治疗预测因子（J-K）话说回来，虽然此次研究提示补充反油酸能够帮助T细胞杀伤肿瘤细胞，但不代表为反油酸洗白，只是指出补充反油酸或可作为癌症免疫治疗中增强疗效的一种新策略。反油酸是一种常见于氢化植物油内的反式长链脂肪酸，长期摄入反油酸可能增加患冠心病和动脉硬化等心血管疾病的风险！总之，这项研究帮助我们更加深入地了解长链脂肪酸代谢对于抗肿瘤免疫反应的影响，揭示了肿瘤细胞内调节MHC-I表达的ASCL5-NLRC5信号通路。参考文献：[1]Sun L, Ma Z, Zhao X, et alLRP11 promotes stem-like T cells via MAPK13-mediated TCF1 phosphorylation, enhancing anti-PD1 immunotherapyJournal for ImmunoTherapy of Cancer 2024;12:e008367. doi: 10.1136/jitc-2023-008367[2]https://www-cell-com.libproxy1.nus.edu.sg/cell-metabolism/abstract/S1550-4131(24)00012-3本文作者丨张艾迪

免疫疗法