Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA.
Biomolecules. 2013 Aug 12;3(3):481-513. doi: 10.3390/biom3030481.
Head and neck squamous cell carcinoma (HNSCC) has a high reoccurrence rate and an extremely low survival rate. There is limited availability of effective therapies to reduce the rate of recurrence, resulting in high morbidity and mortality of advanced cases. Late presentation, delay in detection of lesions, and a high rate of metastasis make HNSCC a devastating disease. This review offers insight into the role of sphingosine kinase-1 (SphK1), a key enzyme in sphingolipid metabolism, in HNSCC. Sphingolipids not only play a structural role in cellular membranes, but also modulate cell signal transduction pathways to influence biological outcomes such as senescence, differentiation, apoptosis, migration, proliferation, and angiogenesis. SphK1 is a critical regulator of the delicate balance between proliferation and apoptosis. The highest expression of SphK1 is found in the advanced stage of disease, and there is a positive correlation between SphK1 expression and recurrent tumors. On the other hand, silencing SphK1 reduces HNSCC tumor growth and sensitizes tumors to radiation-induced death. Thus, SphK1 plays an important and influential role in determining HNSCC proliferation and metastasis. We discuss roles of SphK1 and other sphingolipids in HNSCC development and therapeutic strategies against HNSCC.
头颈部鳞状细胞癌（HNSCC）具有高复发率和极低的生存率。目前有效的治疗方法有限，无法降低复发率，导致晚期病例的发病率和死亡率居高不下。晚期表现、病变检测延迟以及高转移率使 HNSCC 成为一种毁灭性疾病。本综述探讨了鞘氨醇激酶-1（SphK1）在 HNSCC 中的作用，SphK1 是鞘脂代谢中的关键酶。鞘脂不仅在细胞膜中起结构作用，还调节细胞信号转导途径，影响生物学结果，如衰老、分化、凋亡、迁移、增殖和血管生成。SphK1 是增殖和凋亡之间微妙平衡的关键调节剂。SphK1 的最高表达存在于疾病的晚期，并且 SphK1 表达与复发性肿瘤之间存在正相关。另一方面，沉默 SphK1 可减少 HNSCC 肿瘤生长并使肿瘤对辐射诱导的死亡敏感。因此，SphK1 在决定 HNSCC 增殖和转移方面起着重要而有影响力的作用。我们讨论了 SphK1 和其他鞘脂在 HNSCC 发展中的作用以及针对 HNSCC 的治疗策略。
