Ask about this productRelated genes to: SPHK1 antibody
- Gene:
- SPHK1 NIH gene
- Name:
- sphingosine kinase 1
- Previous symbol:
- -
- Synonyms:
- SPHK
- Chromosome:
- 17q25.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-01
- Date modifiied:
- 2015-08-26
Related products to: SPHK1 antibody
Related articles to: SPHK1 antibody
- The SPHKS/S1P pathway has a complex yet close association with the progression of diabetic retinopathy (DR). Oxymatrine (OMT), is believed to potentially regulate this pathway; however, systematic clinical evidence remains insufficient. - Source: PubMed
Publication date: 2026/04/24
Xu JinLi YanQi Ge-YaoFeng JuanWang Fei - Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits perineural invasion (PNI), a clinicopathologic feature strongly associated with local recurrence and poor survival, yet lacking effective targeted interventions. By integrating patient cohorts with single-cell and bulk transcriptomics, multiplex immunofluorescence, and functional assays, this study defines a stromal-tumor signaling axis facilitating neural invasion. Cancer-associated fibroblasts (CAFs), particularly a myofibroblastic CAF-enriched population, upregulate sphingosine kinase 1 (SPHK1) and increase secretion of sphingosine-1-phosphate (S1P), which activates sphingosine-1-phosphate receptor 3 (S1PR3)/JNK/JUN signaling to transcriptionally induce MAL-like protein (MALL) in cancer cells. MALL binds to syndecan-4 (SDC4) and promotes its recycling to the plasma membrane, thereby increasing surface SDC4 abundance. This MALL-SDC4 program promotes RhoA/phosphorylated myosin light chain 2 (p-MLC2)-dependent amoeboid motility and sensitizes cancer cells to Schwann cell-derived pleiotrophin, strengthening directed neural invasion. Disruption of the axis through SPHK1 knockdown in CAFs, genetic perturbation of MALL or SDC4 in cancer cells, or adeno-associated virus-mediated SPHK1 or SDC4 knockdown in KPC (Kras; Trp53; Pdx1-Cre) mice significantly reduces PNI and tumor burden. These findings uncover a metabolite-driven MALL-SDC4 program connecting stromal metabolism to neural invasion, and identify promising therapeutic targets for PDAC. - Source: PubMed
Publication date: 2026/04/22
Peng WangCao MengdieHuang HaiBai ShuyaLiu LuyaoLiang JingwenCui HaochenZhou QiaodanChen ShiruJiang JiameiLiu LuoxiaLuan ZhouChen WeiXiong SiWang RonghuaCheng BinZhao Yuchong - Lung adenocarcinoma (LUAD) exhibits poor prognosis partly due to dysregulated calcium signaling. Here, we integrated bulk RNA-seq (TCGA/LUAD, n = 440) and single-cell sequencing (GSE131907) to identify calmodulin-related prognostic genes. Differential expression analysis and LASSO-Cox regression identified SPHK1 and ASPM as independent predictors of overall survival (HR = 1.52/1.47, < 0.001). A risk model incorporating these genes stratified patients into high/low-risk groups with distinct clinical outcomes (3-year AUC = 0.83). High-risk patients showed elevated γδ T cells and TIDE scores, while SPHK1/ASPM expression correlated with an immunosuppressive myeloid phenotype and M2-like polarization. Single-cell analysis revealed SPHK1-ASPM myeloid cells dominated in early differentiation stages, with pseudo-time trajectories indicating SPHK1 downregulation and ASPM upregulation during myeloid maturation. Multiplex immunofluorescence validated co-localization of SPHK1/ASPM with MPO myeloid cells in tumor tissues. Importantly, the MPOSPHK1/ASPM myeloid compartment was significantly enriched in anti-PD-1 non-responders ( < 0.05). Our study establishes a calcium signaling-based prognostic signature, uncovers myeloid SPHK1/ASPM as drivers of immunosuppression, and provides a potential biomarker for immunotherapy stratification. - Source: PubMed
Publication date: 2026/03/25
Lin ZhouyanAo MinshuHu YueYu ZiyanLu MengyuDong YuchaoBai ChongGuo Meng - Studies have shown that M1 polarization of macrophages plays a crucial role in pathogenesis of acute pancreatitis (AP), although the underlying mechanisms remain incompletely understood. In this study, an AP model was induced in mice using caerulein or L-arginine, while an AP model was established by treating pancreatic acinar cells (PACs) with cholecystokinin (CCK). We observed a significant upregulation of SphK1/S1P in both CCK-treated PACs and the pancreatic tissue of AP mice. In contrast, inflammation and M1 macrophage polarization were markedly attenuated in SphK1 AP mice and upon treatment with pharmacological inhibitors targeting SphK1 or S1PR2. Similarly, M1 polarization of macrophages was notably induced by injured pancreatic acinar cells (iPACs), but this effect was suppressed by SphK1 knockdown or inhibition. Mechanistically, S1P derived from iPACs specifically bound to S1PR2 on macrophages, activating PI3K/JNK and ERK pathways to induce M1 polarization. Moreover, TNF-α secreted by M1 macrophages enhanced SphK1 transcription in PACs through NF-κB activation, forming a positive feedback loop between iPACs and macrophage M1 polarization. Collectively, our findings reveal that the SphK1/S1P/S1PR2/TNF-α axis mediates a reciprocal interaction between iPACs and M1 macrophages, which significantly contributes to AP pathogenesis. - Source: PubMed
Publication date: 2026/03/25
Wang JieZhao GuangyuHu PingHan ShengboHu YuhangZeng ZhuLi YangZhao YongHuang YanZhuo WenfengLv GuozhengWang HongdaZhao Gang - Dysregulated myometrial contractility contributes to obstetric complications. Sphingosine-1-phosphate (S1P), a bioactive lipid, modulates inflammation and smooth muscle contractility, including uterine contractility. However, its metabolic dynamics during pregnancy are poorly characterized. This study profiled S1P metabolic enzymes and receptors, and quantified sphingolipid metabolites in human gestational tissues across pregnancy. - Source: PubMed
Publication date: 2026/03/28
Mbadhi Magdaleena NaemiFujiwara HidejiGill RuthMitchum Kaci TLin Zixi CiciRaghuraman NandiniFrolova Antonina I