ArticleCancer gene therapy2024
SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.
Article in Cancer gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- USP17L2 Regulates SphK1 Ubiquitination and Stability during Autophagy and Pyroptosis in Mycoplasma Pneumoniae Pneumonia.Applied biochemistry and biotechnology · 2026Article
- Review
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- The emerging role of SPHK1 at the immune-metabolic interface: a pan-cancer integrative analysis.Scientific reports · 2026Article
- Gut microbial metabolites in colorectal cancer: dual roles in tumorigenesis, immune crosstalk, and therapeutic innovation.Frontiers in cellular and infection microbiology · 2026Review
- Ubiquitination mediated by RING-type E3 ligases in the progression of digestive system tumors: mechanistic insights and potential therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Sodium butyrate-induced autophagy in colorectal cancer unveils the Ca²⁺/CaMKKβ signaling pathway as a potential therapeutic target.Scientific reports · 2025Article
- Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells.Pharmaceutical science advances · 2025Article
- Crosstalk Between Allergic Inflammation and Autophagy.International journal of molecular sciences · 2025Review
- Targeting SPHK1 in macrophages remodels the tumor microenvironment and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer liver metastasis.Cancer communications (London, England) · 2025Article
- Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer.Journal of cellular and molecular medicine · 2025Article
- Sphingosine kinase 1 promotes M2 macrophage infiltration and enhances glioma cell migration via the JAK2/STAT3 pathway.Scientific reports · 2025Article
- Sphingosine-1-phosphate stimulates colorectal cancer tumor microenvironment angiogenesis and induces macrophage polarization via macrophage migration inhibitory factor.Frontiers in immunology · 2025Article
- [Sphingosine kinase-1 regulates migration and invasion of gastric cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- PRMT6 facilitates EZH2 protein stability by inhibiting TRAF6-mediated ubiquitination degradation to promote glioblastoma cell invasion and migration.Cell death & disease · 2024Article
- SPHK1 promotes HNSCC immune evasion by regulating the MMP1-PD-L1 axis.Theranostics · 2024Article
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9 authors at 1 institution in 1 country.
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Abstract
A sphingolipid metabolite regulator, sphingosine kinase 1 (SPHK1), plays a critical role in the development of colorectal cancer (CRC). Studies have demonstrated that invasion and metastasis of CRC are promoted by SPHK1-driven autophagy. However, the exact mechanism of SPHK1 drives autophagy to promote tumor progression remains unclear. Here, immunohistochemical detection showed the expression of SPHK1 and tumor necrosis factor receptor-associated factor-6 (TRAF6) in human CRC tissues was stronger than in adjacent normal tissues, they were both associated with distance metastasis. It was discovered that knockdown of SPHK1 reduced the expression of TRAF6, inhibited autophagy, and inhibited the growth and metastasis of CRC cells in vitro. Moreover, the effects of SPHK1-downregulating were reversed by overexpression of TRAF6 in CRC cells transfected by double-gene. Overexpression of SPHK1 and TRAF6 promoted the expression of autophagy protein LC3 and Vimentin, while downregulated the expression of autophagy protein P62 and E-cadherin. The expression of autophagy-related ubiquitination protein ULK1 and Ubiquitin protein were significantly upregulated in TRAF6-overexpressed CRC cells. In addition, autophagy inhibitor 3-methyladenine (3MA) significantly inhibited the metastasis-promoting effect of SPHK1 and TRAF6, suppressed the expression of LC3 and Vimentin, and promoted the expression of P62 and E-cadherin, in CRC cells. Immunofluorescence staining showed SPHK1 and TRAF6 were co-localized in HT29 CRC cell membrane and cytoplasm. Immunoprecipitation detection showed SPHK1 was efficiently combined with the endogenous TRAF6, and the interaction was also detected reciprocally. Additionally, proteasome inhibitor MG132 treatment upregulated the expression of TRAF6 and the level of Ubiquitin protein, in SPHK1-downregulating CRC cells. These results reveal that SPHK1 potentiates CRC progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination. SPHK1-TRAF6-ULK1 signaling axis is critical to the progression of CRC and provides a new strategy for the therapeutic control of CRC.
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