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
- Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy with a poor prognosis, characterized by dedifferentiation and aberrant angiogenesis. Through integrated analysis of TCGA and GEO transcriptomic data and single-cell RNA sequencing, this study identified significant enrichment of angiogenesis-related genes (ARGs), particularly sphingosine kinase 1 (SPHK1), in malignant cell subpopulations of ATC. Functional investigations revealed that alkaline ceramidase 3 (ACER3) cooperates with SPHK1 within the sphingolipid metabolic pathway to promote ATC progression. The SPHK1-specific inhibitor PF543 suppresses the activity of this key protein, thereby exhibiting potential therapeutic effects. To address the poor aqueous solubility and limited targeting ability of PF543, we constructed biomimetic nanoparticles (CMOE@PLGA@PF543) coated with S1PR1-overexpressing cancer cell membranes (CMOE), enabling tumor-specific targeting through the sphingosine-1-phosphate (S1P) and sphingosine-1-phosphate receptor 1 (S1PR1) ligand-receptor interaction. In vitro, PF543 downregulated SPHK1 expression and induced apoptosis in ATC cells. In vivo, CMOE@PLGA@PF543 exhibited enhanced tumor-targeting accumulation, excellent biosafety, and potent inhibition of tumor growth by suppressing the ACER3/SPHK1/S1P axis. These findings reveal a novel molecular mechanism driving ATC progression and offer a targeted nanotherapeutic strategy with strong potential for clinical translation. - Source: PubMed
Publication date: 2026/05/11
Bai YangChen JiaqiLin HaipingMa WeikeZhu MengtingZhang YuxiangDuan YantingXu JiajieGe Minghua - Lymph node metastasis (LNM) is a pivotal determinant of poor prognosis in ovarian cancer (OC), yet how tumor-intrinsic programs remodel the microenvironment to enable spread remains unclear.Here, we identify the transcription factor mesenchymal homeobox 1 (MEOX1) as an upstream coordinator, whose overexpression associates with LNM, increased lymphatic density, and poor survival based on integrative analyses of public datasets and our 113-patient cohort. In an in vivo LNM model, MEOX1 overexpression enhances tumor burden, lymphatic vessel density, and LNM, whereas tumor-conditioned medium does not directly activate lymphatic endothelial cells (LECs), implicating stromal intermediates. Spatial transcriptomic and immunostaining analyses confirmed cancer-associated fibroblast (CAF)-LEC proximity and vascular endothelial growth factor-C (VEGF-C) localization within CAFs, supporting a CAF-dependent lymphangiogenic route. Mechanistically, MEOX1 binds the sphingosine kinase 1 (SPHK1) promoter to activate sphingosine-1-phosphate (S1P) synthesis, driving a dual autocrine-paracrine program: sphingosine-1-phosphate receptor 3 (S1PR3)-dependent signaling promotes tumor proliferation/migration, while S1P/S1PR1 reprograms fibroblasts into VEGF-C-secreting, alpha-smooth muscle actin (α-SMA)-positive CAFs that stimulate lymphangiogenesis and LNM; SPHK1 inhibition blunts these phenotypes, whereas S1P supplementation restores them. These findings provide novel insights into lymphatic metastasis and demonstrate that metastatic competence depends not only on intrinsic tumor aggressiveness but also on the acquired ability to construct a pro-dissemination niche. - Source: PubMed
Publication date: 2026/05/10
Li JiajiaZhi XiulingLin QianhanSun YatingSun YihuaAbudousalamu ZulimireXue MengyangZheng ChangLi XiaotianYao LiangqingChen Mo - Although chemotherapy-induced bone loss is well-recognized during breast cancer treatment, the underlying mechanism remains to be further elucidated, especially in patients with obesity. In this study, the objective was to investigate the impact of genomic silencing and pharmacological inhibition of S1P synthesis on bone loss in doxorubicin-induced obese breast cancer mice. In vitro study, upon the treatment of doxorubicin combined with palmitic acid, the S1P generated by 4T1 cells was significantly increased, resulting in an increase in osteoclastogenesis by activating the S1PR1/p-STAT3/NFATc-1 pathway in bone marrow-derived macrophages. In vivo study, pharmacological intervention with Sphingosine kinases (SPHK) antagonist SKI II or biological inhibition with SPHK1 and SPHK2 short hairpin RNA significantly reduced S1P production and rescued the obese breast cancer-bearing mice from doxorubicin-induced bone loss, manifested by the decreased osteoclastogenesis and recovered bone microarchitecture. Similarly, the administration of the S1PR1 antagonist FTY720 also alleviated bone loss in the breast cancer-bearing mice fed a high-fat diet. These studies indicate that genetic silencing and pharmacological inhibition can suppress S1P-dependent bone loss in doxorubicin-induced obese breast cancer mice. S1P shows promise as a potential drug target for preventing chemotherapy-induced bone loss in patients. - Source: PubMed
Publication date: 2026/03/30
Zhang YuShen HaoNiu JunjieHuang YingkangZhu CanWang YiChen YidaCheng XinyiYang HuilinZhang XianrongChen HaoZhang HongboShi Qin - MS is a lifelong autoimmune disorder striking the central nervous system (CNS). Despite the currently used disease-modifying therapies, patients are exposed to persistent neuropathy, pinpointing the need for supportive therapy. Neurotropic vitamins B1, B6 and B12 have been used to offer relief from immunological and neurological MS manifestations. This study aimed to provide some mechanistic insights into the relationship of B1/B6/B12 vitamin supplementation with the development of MS regarding lipid metabolism and epigenetics. In this cross-sectional observational study, blood samples were obtained from 53 MS patients, including 25 patients who had received daily vitamin B1/B6/B12 supplementation for over six months and 28 patients without supplementation. Plasma sphingosine-1-phosphate (S1P) and S1P receptor-1 (S1PR1) levels, lipid profile, and gene expression of ApoA1, sphingosine kinases 1&2 (SPHK1&2), S1PR1, as well as the lnc RNAs APOA1-AS and LISPR1 were evaluated. Gene ontology and KEGG pathway enrichment analyses were conducted. Vitamin B1/B6/B12 supplementation was associated with a more favorable lipid profile. Supplemented patients also exhibited higher ApoA1 and lower APOA1-AS expression compared with non-supplemented patients. Additionally, vitamin B1/B6/B12 supplementation was associated with lower expression levels of SPHK1, SPHK2, LISPR1, and S1PR1, and reduced circulating S1P concentrations. These findings imply significant associations between long-term vitamin B1/B6/B12 supplementation, alterations in lipid-related markers and sphingosine-associated signaling in MS patients. However, the observational design, selection bias and small sample size limit causal inference and may not fully capture the heterogeneity of MS population. Besides, supplement adherence was self-reported and not objectively verified, and circulating vitamin levels were not measured. - Source: PubMed
Publication date: 2026/05/01
Mehana Noha AGhaiad Heba RNooh Mohammed MAmer Mai AEl-Ghoneimy Lobna TalaatSafwat Maheera H - Sphingosine-1-phosphate (S1P) is a critical bioactive lipid mediator that regulates essential cellular processes-including proliferation, survival, migration, and inflammation-through binding to its cognate receptors (S1PRs) on the cell membrane or via direct intracellular actions. Sphingosine Kinase 2 (SphK2) has thus emerged as a promising therapeutic target. In this study, we designed and synthesized a novel series of SphK2 inhibitors (Q-series) based on the lead compound K145. Among these, compounds Q20 (IC = 2.6 ± 0.46 μM), Q24 (IC = 4.27 ± 1.51 μM), and Q25 (IC = 6.25 ± 0.62 μM) displayed potent and selective inhibition of SphK2, while showing negligible activity against SphK1 (IC > 50 μM). Notably, Q25 exhibited significant anti-proliferative effects against multiple colorectal cancer cell lines (LOVO, SW480, SW620, HT-29), with IC values of 8.09 ± 4.36, 7.77 ± 2.48, 7.38 ± 3.41, and 6.41 ± 2.46 μM, respectively. Mechanistically, Q25 induced S-phase cell cycle arrest and apoptosis. The Q-series compounds (Q20, Q24, Q25) also demonstrated favorable metabolic stability in human liver microsomes, characterized by prolonged half-lives (T > 90 min), low intrinsic clearance (CLint(mic) < 15 μL/min/mg), and high parent compound recovery (∼50% remaining after incubation). In vivo pharmacokinetic studies in mice indicated that Q25 is rapidly metabolized, classified as a high-clearance compound, and undergoes extrahepatic elimination. In a SW480 xenograft mouse model, Q25 effectively inhibited tumor growth without observable toxicity. Western blot analysis suggested that its anti-tumor effect is associated with reduced S1P production and subsequent suppression of the NF-κB pathway. In summary, these findings identify Q25 as a promising, selective SphK2 inhibitor worthy of further development as an anticancer agent. - Source: PubMed
Publication date: 2026/04/26
Liu JunruShi XiujuanYang XinmeiZhao XiaodongHuang FuxunLi ZhaoyangLiu YuanyuanGao YuqiFeng JingtongQu ZhiqiangYi ChenghuaYang YeLiang ZihanYao QingqiangLiu Bo