ArticleAutophagy2017
SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 130 citations in OpenAlex.
- Targeting Iron Regulatory Protein 2 in Tumor-associated Macrophages Activates Antitumor Immunity in NSCLC via Modulating SphK1-PD-L1 Axis.International journal of biological sciences · 2026Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- ASS1 inhibits liver cancer by promoting CAD ubiquitination and reversing the urea cycle and pyrimidine synthesis imbalance.Hepatology communications · 2025Article
- TMBIM1 promotes epithelial mesenchymal transition by accelerating autophagic degradation of E-cadherin in glioblastoma.Scientific reports · 2025Article
- Epithelial-to-mesenchymal transition and live cell extrusion contribute to measles virus release from human airway epithelia.Journal of virology · 2025Article
- Potential Modulatory Role of Phoenixin-14 in Epithelial-Mesenchymal Transition of Endometriotic 12Z Cells.Biomedicines · 2025Article
- Integrated multi-optosis model for pan-cancer candidate biomarker and therapy target discovery.Frontiers in bioinformatics · 2025Article
- SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.Cell death & disease · 2024Article
- Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.Molecular medicine (Cambridge, Mass.) · 2024Article
- Review
- SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination.Cancer gene therapy · 2024Article
- PAK inhibitor FRAX486 decreases the metastatic potential of triple-negative breast cancer cells by blocking autophagy.British journal of cancer · 2024Article
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Unlocking New Avenues in Breast Cancer Treatment: The Synergy of Kinase Inhibitors and Immunotherapy.Cancers · 2023Review
- Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions.International journal of molecular sciences · 2023Review
- The role of sphingosine-1-phosphate in autophagy and related disorders.Cell death discovery · 2023Review
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- miR‑137 is a diagnostic tumor‑suppressive miRNA that targets SPHK2 to promote M1‑type tumor‑associated macrophage polarization.Experimental and therapeutic medicine · 2023Article
- Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we reported that SPHK1 induced the epithelial-mesenchymal transition (EMT) by accelerating CDH1/E-cadherin lysosomal degradation and facilitating the invasion and metastasis of HepG2 cells. Initially, we found that SPHK1 promoted cell migration and invasion and induced the EMT process through decreasing the expression of CDH1, which is an epithelial marker. Furthermore, SPHK1 accelerated the lysosomal degradation of CDH1 to induce EMT, which depended on TRAF2 (TNF receptor associated factor 2)-mediated macroautophagy/autophagy activation. In addition, the inhibition of autophagy recovered CDH1 expression and reduced cell migration and invasion through delaying the degradation of CDH1 in SPHK1-overexpressing cells. Moreover, the overexpression of SPHK1 produced intracellular sphingosine-1-phosphate (S1P). In response to S1P stimulation, TRAF2 bound to BECN1/Beclin 1 and catalyzed the lysine 63-linked ubiquitination of BECN1 for triggering autophagy. The deletion of the RING domain of TRAF2 inhibited autophagy and the interaction of BECN1 and TRAF2. Our findings define a novel mechanism responsible for the regulation of the EMT via SPHK1-TRAF2-BECN1-CDH1 signal cascades in HCC cells. Our work indicates that the blockage of SPHK1 activity to attenuate autophagy may be a promising strategy for the prevention and treatment of HCC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.