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Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells

  • Authors:
    • Wenlu Zhang
    • Chunyan Xu
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China, Department of Gastroenterology and Institute of Digestive Diseases, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 73
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    Published online on: January 23, 2025
       https://doi.org/10.3892/mmr.2025.13438
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Abstract

Exosomes are small extracellular vesicles that are naturally released into body fluids by cells. They are rich in bioactive molecules such as proteins. Sphingosine kinase 1 (SphK1) is an important potential drug target for the treatment of cancer due to its functions to regulate cancer cell migration, growth, apoptosis and angiogenesis. Tumor exosomes abundantly surround primary tumors, exchanging and transferring information between cells and modulating cancer progression. Given the importance of exosomes, the involvement of exosomal SphK1 from colorectal cancer (CRC) cells in the migration of these cells and the activation of hepatic stellate cells was investigated. Firstly, the plasma exosomal SphK1 protein expression, tested by ELISA, was compared between patients with CRC without metastasis and those with liver metastasis. The results revealed that plasma exosomal SphK1 levels were significantly upregulated in patients with liver metastasis of CRC. Secondly, exosomes with different expression levels of SphK1, which were regulated by cell transfection, were isolated from CRC cells to evaluate their effect on the expression levels of E‑cadherin and vimentin in these cells, as assessed by western blotting. The results demonstrated that depletion of exosomal SphK1 partially reversed the exosome‑induced migration of CRC cells, and caused decreased vimentin and increased E‑cadherin levels. Thirdly, the effects of exosomes from CRC cells, with different expression levels of SphK1, on hepatic stellate cell activation were investigated, with α‑SMA, TNF‑α and TGF‑β levels assessed by western blotting in LX‑2 cells. Moreover, AKT and phosphorylated (p‑)AKT levels were also assessed by western blotting. The results revealed that exosomes activated hepatic stellate cells by upregulating p‑AKT, and depletion of exosomal SphK1 partially reversed this effect. Furthermore, the application of an AKT agonist reversed the inhibition of hepatic stellate cell activation, which was induced by the depletion of exosomal SphK1. Finally, investigation of cell viability, analyzed by CCK‑8 assay, and assessment of PCNA as a proliferation marker, analyzed by western blot, revealed that the culture supernatant of the activated hepatic stellate cells promoted the viability of CRC cells. Overall, these results demonstrated that exosomal SphK1 increased the migration of CRC cells, and activated hepatic stellate cells by regulating p‑AKT. This suggests that exosomal SphK1 may serve a key role in the migration of CRC cells and potentially the liver metastasis of CRC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W and Xu C: Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells. Mol Med Rep 31: 73, 2025.
APA
Zhang, W., & Xu, C. (2025). Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells. Molecular Medicine Reports, 31, 73. https://doi.org/10.3892/mmr.2025.13438
MLA
Zhang, W., Xu, C."Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells". Molecular Medicine Reports 31.3 (2025): 73.
Chicago
Zhang, W., Xu, C."Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells". Molecular Medicine Reports 31, no. 3 (2025): 73. https://doi.org/10.3892/mmr.2025.13438
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W and Xu C: Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells. Mol Med Rep 31: 73, 2025.
APA
Zhang, W., & Xu, C. (2025). Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells. Molecular Medicine Reports, 31, 73. https://doi.org/10.3892/mmr.2025.13438
MLA
Zhang, W., Xu, C."Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells". Molecular Medicine Reports 31.3 (2025): 73.
Chicago
Zhang, W., Xu, C."Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells". Molecular Medicine Reports 31, no. 3 (2025): 73. https://doi.org/10.3892/mmr.2025.13438
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