ACSL3
- Known as:
- ACSL3
- Catalog number:
- 001046A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACSL3
Related genes to: ACSL3
- Gene:
- ACSL3 NIH gene
- Name:
- acyl-CoA synthetase long chain family member 3
- Previous symbol:
- FACL3
- Synonyms:
- ACS3, PRO2194
- Chromosome:
- 2q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-04-25
- Date modifiied:
- 2019-03-21
Related products to: ACSL3
Related articles to: ACSL3
- Lymph node metastasis in hepatocellular carcinoma depends heavily on lipid metabolic reprogramming, wherein the acyl-CoA synthetase long-chain family members ACSL3 and ACSL4 act as central survival hubs. However, single-target interventions often fail to curb metastasis due to the inherent metabolic plasticity and flexibility of tumors. Here, through retrospective clinical cohort analyses, we discovered that ACSL3 and ACSL4 are markedly co-upregulated in metastatic lymph nodes, driving malignant progression and poor prognosis. Driven by this finding, we engineered a lymph node-targeted nanoplatform (siACSL3/4@Gal-LNP) for the dual-gene inhibition, aiming to modulate lipid metabolism and validate its feasibility as a therapeutic target. Utilizing this platform, we elucidated an integrated metabolic axis comprising the ACSL3-mediated "metabolic shield" for ferroptosis resistance and the ACSL4-driven "metastatic spear" for enhanced invasion. Notably, we found that single-target inhibition of ACSL4 triggers a compensatory upregulation of ACSL3, which decreases the ferroptosis sensitivity of tumor cells. Leveraging this dual-inhibition capability, the siACSL3/4@Gal-LNP nanoplatform effectively overcomes adaptive escape, directly inducing a profound lipid collapse. This intervention reshapes membrane biophysics to suppress invasion and triggers ferroptosis. Concurrently, it depletes Tregs and downregulates PD-L1, effectively reprogramming the immunosuppressive microenvironment toward an immune-active state. Furthermore, we verified that siACSL3/4@Gal-LNP could greatly sensitize metastatic tumors to low-dose radiotherapy by blocking metabolic escape pathways, and markedly overcome tumor cell resistance to ferroptosis. Therefore, this "dismantling shield and breaking spear" strategy effectively disrupts the lipid metabolic plasticity and remodels the immune microenvironment, providing a highly potent and effective therapeutic strategy for lymph node metastatic tumors. - Source: PubMed
Publication date: 2026/10/01
Fu BaixueGao RuiXie ZhizhengLin XueChu KaifeiGong XinyanZou LanbingZhang YuminZhang JiaminLiu JianfengYang Cuihong - Cholangiocarcinoma (CCA) is a biliary epithelial malignancy of relentless lethality, whose therapeutic intractability is inseparable from its radical metabolic reprogramming. Ferroptosis, an iron-catalysed, lipid-hydroperoxide-mediated form of regulated cell death, has emerged as a compelling therapeutic vulnerability in CCA. However, exploiting this vulnerability demands a mechanistic account of how CCA cells engineer their membrane lipidome to escape ferroptotic execution. This review advances the argument that the ratio of monounsaturated fatty acid (MUFA)-containing phosphatidylethanolamines (PEs) to polyunsaturated fatty acid (PUFA)-PEs within the plasma membrane may constitute a principal determinant of ferroptotic fate in CCA, a proposed dynamic equilibrium we term the "ferroptotic rheostat." We synthesise the available lipidomic, metabolomic, and functionally integrated evidence across multiple CCA datasets, centering on the acyl-CoA synthetase long-chain family member 3 (ACSL3)-driven MUFA enrichment of CCA cell membranes as the most direct, although still single-study, CCA-specific evidence for a membrane-lipid-based ferroptosis resistance mechanism. We state at the outset that the rheostat is advanced as a working hypothesis and a proposed model, not as an established mechanism. It rests on a single untargeted lipidomic study in four CCA cell lines, and the membrane MUFA-PE: PUFA-PE ratio has not been measured directly in human CCA tumour tissue by any published study. We further contextualise how de novo lipogenesis through the fatty acid synthase (FASN)-stearoyl-CoA desaturase-1 (SCD1) axis, ATP-citrate lyase (ACLY)-dependent acetyl-CoA supply, and CCA-specific bile acid-farnesoid X receptor (FXR)-lipid metabolism crosstalk collectively tune rheostat position. We emphasise, however, that apart from the ACSL3-MUFA axis the individual links of this framework are at present supported largely by transcriptomic, bioinformatic, or cross-tumour evidence rather than by direct redox lipidomic measurement in human CCA tissue, and we therefore flag these steps explicitly as hypotheses throughout. The oncometabolic consequences of isocitrate dehydrogenase (IDH1/2) mutations, mediated through 2-hydroxyglutarate (2-HG) and NADPH depletion, are discussed as a genetically defined entry point for ferroptosis sensitisation in a 15-20% iCCA subset. We conclude by outlining priority research gaps, including the systematic application of redox phospholipidomics and spatial lipidomics to human CCA biospecimens, and set out the measurements that would be required to test, refute, or refine the proposed model before a lipid-centric intervention strategy could be considered in CCA. - Source: PubMed
Publication date: 2026/09/27
Köse-Demirtaş BüşraKurtoğlu Duygu - Tumor metastasis and drug resistance are the leading causes of mortality in patients with colorectal cancer (CRC). Protein palmitoylation exerts a pivotal role in the metabolic reprogramming across various malignancies. However, the precise mechanisms underlying its contribution to CRC metastasis and drug resistance via lipid metabolism reprogramming remain elusive. Therefore, this study aimed to elucidate the specific role of ZDHHC9 in conferring Cetuximab resistance in CRC. Initial phenotypic screening with the broad-spectrum inhibitor 2-BP implicated palmitoylation in Cetuximab resistance. Subsequently, targeted genetic experiments identified ZDHHC9 as the specific molecular driver. Furthermore, ZDHHC9 was significantly upregulated in CRC tissues and strongly correlated with poor patient prognosis. Subsequent in vitro and in vivo experiments demonstrated that ZDHHC9 functionally promoted Cetuximab resistance in CRC. Mechanistically, ZDHHC9 physically interacted with ACSL3 and enhanced its palmitoylation, thereby driving the malignant progression of CRC. Moreover, we identified cysteine 468 (C468) as the critical residue responsible for the palmitoylation of ACSL3. Notably, ectopic overexpression of ACSL3 effectively rescued the suppression of CRC cell proliferation induced by ZDHHC9 depletion. In conclusion, our findings establish the ZDHHC9-ACSL3 axis as a preclinically validated resistance driver and an actionable metabolic vulnerability for overcoming Cetuximab resistance in CRC. - Source: PubMed
Publication date: 2026/09/25
Song KunGe ZuyinLin YunxiaoXie ZhaolanWang TiangongHao Jingduo - Previous work has indicated that lipid metabolic reprogramming plays a critical role in gastric cancer (GC) development, yet the underlying molecular mechanisms remain largely undefined. In the present study, we identified a novel lipid metabolism-associated long non-coding RNA, 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 (lncHMGCS1), which is aberrantly upregulated in GC tissues and cell lines. Functional assays demonstrated that lncHMGCS1 overexpression could promote intracellular lipid droplet accumulation, elevate the triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and enhance GC cell proliferation. Mechanistically, lncHMGCS1 can suppress expression of miR-18b-5p, a microRNA that directly targets both lncHMGCS1 and acyl-CoA synthetase long-chain family member 3 (ACSL3). ACSL3 knockdown reversed the oncogenic effects of lncHMGCS1 on GC cells in a miR-18b-5p-dependent manner, highlighting the critical role of the lncHMGCS1-ACSL3 axis in lipid metabolic reprogramming. Collectively, our findings establish lncHMGCS1 as a driver of lipid metabolism and tumorigenesis in GC, laying the groundwork for the development of novel diagnostic and therapeutic targets for managing this disease. - Source: PubMed
Publication date: 2026/09/10
Yang QiangHe YuyangWang LejiaYuan XiaoxiaZhang JingpingChen JinxinJiang GuohuiMa WenrongLu XingtongWei ChenZhang BinDeng ShihaoLuo YaominXiao YangLong KexunXu ChaoyingYin XinqiangJiang Zhen - - Source: PubMed
Publication date: 2026/09/04
Mo QiongNing Yun-Jia