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Article

C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation

  • Authors:
    • Min Hee Kim
    • Joo‑Won Park
    • Eun‑Ji Lee
    • Shin Kim
    • Sun‑Hye Shin
    • Jung‑Hyuck Ahn
    • Yunjae Jung
    • Inkeun Park
    • Woo‑Jae Park
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea, Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea, Department of Immunology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea, Department of Microbiology, College of Medicine, Gachon University, Incheon 21999, Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea , Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, Republic of Korea
  • Pages: 2977-2987
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    Published online on: September 7, 2018
       https://doi.org/10.3892/or.2018.6689
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Abstract

Recently, sphingolipid derivatives, such as ceramide and sphingosine‑1‑phosphate (S1P), have emerged as key modulators in apoptotic cell death and cell proliferation. This study aimed to clarify the underlying signaling pathways of ceramide and S1P involved in breast cancer cell proliferation. Ceramide acyl chain length is determined by six mammalian ceramide synthases (CerS). We overexpressed CerS1 to 6 in MCF‑7 cells to examine whether ceramide signaling propagation varies as a function of acyl chain length. Among the six CerS, only CerS6 overexpression reduced phosphorylation of Akt, S6 kinase (S6K), and extracellular signal‑regulated kinases (ERK) as shown by western blotting. In addition, CerS6 overexpression reduced MCF‑7 cell proliferation. This effect was partially reversed by co‑treatment with MHY1485, an activator of mammalian target of rapamycin (mTOR), demonstrating an important role for the mTOR pathway in the CerS6‑mediated decrease in MCF‑7 cell proliferation. ERK inhibition, but not Akt inhibition, along with mTOR inhibition synergistically reduced MCF‑7 cell proliferation as measured by MTT assay. Notably, the expression of CerS6 and S1P receptor 2 (S1PR2), or CerS6 and sphingosine kinase 1 (SphK1), were negatively correlated according to the invasive breast carcinoma patient cohort in The Cancer Genome Atlas database. In addition, both SphK1 overexpression and S1P addition increased mTOR phosphorylation as shown by ELISA, while S1PR2 inhibition had the inverse effect. These data suggest that CerS6 and SphK1 regulate mTOR signaling in breast cancer cell proliferation. Moreover, mTOR activity can be regulated by the balance between S1P and C16‑ceramide, which is generated by CerS6.
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Copy and paste a formatted citation
Spandidos Publications style
Kim MH, Park JW, Lee EJ, Kim S, Shin SH, Ahn JH, Jung Y, Park I and Park WJ: C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation. Oncol Rep 40: 2977-2987, 2018.
APA
Kim, M.H., Park, J., Lee, E., Kim, S., Shin, S., Ahn, J. ... Park, W. (2018). C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation. Oncology Reports, 40, 2977-2987. https://doi.org/10.3892/or.2018.6689
MLA
Kim, M. H., Park, J., Lee, E., Kim, S., Shin, S., Ahn, J., Jung, Y., Park, I., Park, W."C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation". Oncology Reports 40.5 (2018): 2977-2987.
Chicago
Kim, M. H., Park, J., Lee, E., Kim, S., Shin, S., Ahn, J., Jung, Y., Park, I., Park, W."C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation". Oncology Reports 40, no. 5 (2018): 2977-2987. https://doi.org/10.3892/or.2018.6689
Copy and paste a formatted citation
x
Spandidos Publications style
Kim MH, Park JW, Lee EJ, Kim S, Shin SH, Ahn JH, Jung Y, Park I and Park WJ: C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation. Oncol Rep 40: 2977-2987, 2018.
APA
Kim, M.H., Park, J., Lee, E., Kim, S., Shin, S., Ahn, J. ... Park, W. (2018). C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation. Oncology Reports, 40, 2977-2987. https://doi.org/10.3892/or.2018.6689
MLA
Kim, M. H., Park, J., Lee, E., Kim, S., Shin, S., Ahn, J., Jung, Y., Park, I., Park, W."C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation". Oncology Reports 40.5 (2018): 2977-2987.
Chicago
Kim, M. H., Park, J., Lee, E., Kim, S., Shin, S., Ahn, J., Jung, Y., Park, I., Park, W."C16‑ceramide and sphingosine 1‑phosphate/S1PR2 have opposite effects on cell growth through mTOR signaling pathway regulation". Oncology Reports 40, no. 5 (2018): 2977-2987. https://doi.org/10.3892/or.2018.6689
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