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
- Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. As a predominant immune cell population in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play a critical role in tumor progression and resistance to immune checkpoint inhibitors (ICIs). TAMs can promote either antitumor immunity or immunosuppression depending on their polarization status. Iron regulatory protein 2 (IRP2) is a key regulator of intracellular iron homeostasis and has been reported to be upregulated in several tumor types. However, the role of IRP2 in the TME remains unclear. This study revealed the previously unrecognized role of IRP2 in NSCLC progression and explored its potential as a TAM-directed therapeutic target linked to programmed death-ligand 1 (PD-L1) regulation. We found that IRP2 skewed TAMs toward an immunosuppressive state that promoted tumor cell proliferation and migration, and limited apoptosis. Furthermore, IRP2 may sustain PD-L1 expression in TAMs by limiting sphingosine kinase 1 (SphK1)-associated lysosomal degradation. In conclusion, our findings identify IRP2-dependent maintenance of the immunosuppressive TAM phenotype as a promising therapeutic target in NSCLC. - Source: PubMed
Publication date: 2026/09/03
Ding JiawenCheng QinpeiCheng ChenMei YingYang LiuChen PeilinZheng LeiZhu SuhuaShen KaikaiLi KuanyuLv Tangfeng - Reprogramming of glucose metabolism serves as the driving force behind the abnormal proliferation of fibroblast-like synoviocytes (FLSs), contributing to synovial hyperplasia in Rheumatoid arthritis (RA). However, the underlying mechanisms governing the glycolytic phenotype of RA-FLSs remain unclear. There was a metabolic shift toward glycolysis in synovial tissue of RA patients and CIA rats, as well as in TNF-α-induced MH7A cells. RNA sequencing revealed that pyruvate kinase M2 (PKM2) and sphingosine kinase 1 (SphK1), as differentially expressed glycolysis-related genes, were upregulated in RA synovium. Notably, PKM2 succinylation was significantly elevated in vivo and in vitro, which was attributed to reduced expression of SIRT5 with desuccinylation activity. Succinylation facilitated the conversion of PKM2 from tetramers to dimers. Functionally, this shift promoted glycolysis and cell proliferation, while enhancing mitochondrial fission. Overexpression of SIRT5 weakened the PKM2 succinylation in TNF-α-induced MH7A cells. It was confirmed that Lys311 was a crucial site for PKM2 succinylation modification in MH7A cells. Aberrant SphK1 activation, characterized by increased membrane targeting, was observed both in vivo and in vitro. SphK1 knockdown inhibited this membrane targeting and reduced PKM2 succinylation, concomitant with reactivation of the PKA/PGC1α/SIRT5 signaling axis. In addition, SphK1 inhibition attenuated PKM2 succinylation in synovial tissue and FLSs from CIA rats via upregulating the PKA/PGC1α/SIRT5 signaling axis, resulting in downregulated glycolysis. Overall, PKM2 succinylation promotes glycolysis in RA-FLSs and induces synovial hyperplasia, and this process is regulated by SphK1 membrane targeting, highlighting a novel strategy for safe and effective treatment of RA. - Source: PubMed
Publication date: 2026/09/26
Gan PeirongLi BingZhu YulongPang JingWang ShihanDeng RanBu YanhongWang YanRong GenxiangZhu YanWu Hong - Endometrial cancer (EC) is the most common gynecological malignancy in postmenopausal women. Patients with low estrogen receptor alpha (ERα) expression frequently develop aggressive pathological subtypes and have poor prognosis. The role of estradiol (E2) in ERα-low EC remains poorly understood. This study investigated the tumor-promoting effects of E2 using clinical data, in vitro functional assays, and a mouse xenograft model. We found that serum E2 levels were elevated in ERα-low patients, of whom 67.7% showed high tumor expression of G protein-coupled estrogen receptor (GPER). High GPER expression correlated with increased E2 levels, enhanced sphingosine kinase 1 (SphK1) activity, and higher Ki67 proliferation index. In vitro, E2 promoted proliferation, migration, and invasion of HEC-1A cells (low ERα, high GPER). These effects were suppressed by pharmacological inhibition or siRNA knockdown of GPER or SphK1. Mechanistically, E2 activated the ERK1/2 pathway via the GPER/SphK1 axis, leading to upregulation of Cyclin D1, Cyclin E1, and MMP-9. In vivo, E2 stimulated xenograft tumor growth, an effect mitigated by inhibitors of GPER, SphK1, and ERK. Our findings demonstrate that E2 drives progression of ERα-low endometrial cancer through the GPER/SphK1 signaling pathway, revealing potential therapeutic targets for this high-risk subgroup. - Source: PubMed
Wang XiuwenSun HaofeiWen XinXin WeiweiHu ZhandongZhao ZhongweiZhang Lizhi - This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. - Source: PubMed
Publication date: 2026/09/04
Lu ChenyiYang XinyiYang Xin - Neutrophils are increasingly recognised as immunosuppressive drivers of hepatocellular carcinoma (HCC), yet their persistence in the oxidative, lipid-rich tumour microenvironment remains poorly understood. - Source: PubMed
Publication date: 2026/09/07
Ma JunWu TongChen DiyuZhu CanHuang ShanheDu KeyiPeng ChuanhuiChen JunruChen YunhaoXie HaiyangZhang FengChen JianzhongZheng ShusenWu Jian