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Targeting Sphingolipid Metabolism as a Therapeutic Strategy in Cancer Treatment
Alhaji H Janneh1, Besim Ogretmen1
1Hollings Cancer Center, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Abstract:
Sphingolipids are bioactive molecules that have key roles in regulating tumor cell death and survival through, in part, the functional roles of ceramide accumulation and sphingosine-1-phosphate (S1P) production, respectively. Mechanistic studies using cell lines, mouse models, or human tumors have revealed crucial roles of sphingolipid metabolic signaling in regulating tumor progression in response to anticancer therapy. Specifically, studies to understand ceramide and S1P production pathways with their downstream targets have provided novel therapeutic strategies for cancer treatment. In this review, we present recent evidence of the critical roles of sphingolipids and their metabolic enzymes in regulating tumor progression via mechanisms involving cell death or survival. The roles of S1P in enabling tumor growth/metastasis and conferring cancer resistance to existing therapeutics are also highlighted. Additionally, using the publicly available transcriptomic database, we assess the prognostic values of key sphingolipid enzymes on the overall survival of patients with different malignancies and present studies that highlight their clinical implications for anticancer treatment.
Insights
Sphingolipids regulate cancer cell death and survival. Targeting ceramide and sphingosine-1-phosphate (S1P) pathways offers novel anticancer strategies and impacts treatment resistance.
Area of Science:
- Biochemistry
- Cancer Biology
- Molecular Oncology
Background:
- Sphingolipids, including ceramide and sphingosine-1-phosphate (S1P), are critical bioactive lipids involved in cellular processes.
- Dysregulation of sphingolipid metabolism is implicated in tumor progression and response to therapy.
- Understanding these pathways is key to developing new cancer treatments.
Purpose of the Study:
- To review the roles of sphingolipids and their metabolic enzymes in cancer progression.
- To highlight the impact of S1P on tumor growth, metastasis, and therapeutic resistance.
- To assess the prognostic value of sphingolipid enzymes in various malignancies.
Main Methods:
- Review of mechanistic studies using cell lines, mouse models, and human tumors.
- Analysis of sphingolipid metabolic pathways and their downstream targets.
- Assessment of transcriptomic data from public databases for prognostic value of key enzymes.
Main Results:
- Sphingolipids critically regulate tumor cell death and survival.
- S1P production promotes tumor growth, metastasis, and resistance to anticancer therapies.
- Key sphingolipid enzymes show prognostic value across different cancers.
Conclusions:
- Sphingolipid metabolic signaling is a crucial determinant of tumor progression and therapeutic response.
- Targeting sphingolipid pathways presents promising therapeutic strategies for cancer treatment.
- Sphingolipid enzymes serve as potential biomarkers for patient prognosis and treatment selection.
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