Janneh Alhaji H, Ogretmen Besim
Hollings Cancer Center, Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Cancers (Basel). 2022 Apr 27;14(9):2183. doi: 10.3390/cancers14092183.
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.
鞘脂是生物活性分子，在调节肿瘤细胞死亡和存活方面发挥关键作用，部分原因分别是神经酰胺积累和鞘氨醇-1-磷酸（S1P）产生的功能作用。使用细胞系、小鼠模型或人类肿瘤进行的机制研究揭示了鞘脂代谢信号在调节肿瘤对抗癌治疗反应的进展中的关键作用。具体而言，了解神经酰胺和S1P产生途径及其下游靶点的研究为癌症治疗提供了新的治疗策略。在本综述中，我们展示了鞘脂及其代谢酶通过涉及细胞死亡或存活的机制在调节肿瘤进展中的关键作用的最新证据。还强调了S1P在促进肿瘤生长/转移以及赋予癌症对现有疗法的抗性方面的作用。此外，利用公开可用的转录组数据库，我们评估了关键鞘脂酶对不同恶性肿瘤患者总生存的预后价值，并展示了突出其在抗癌治疗中临床意义的研究。
