Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, People's Republic of China.
Cell Death Dis. 2018 Jan 19;9(2):54. doi: 10.1038/s41419-017-0088-2.
Neuroblastoma (NB) is the most common malignant tumor in infancy and most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low-risk and intermediate-risk NB can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discover new therapeutic targets for NB. Polo-like kinase 4 (PLK4), one of the polo-like kinase family members, is an important regulator of centriole replication. The aberrant expression of PLK4 was found in several cancers and a recent study has unraveled a novel function of PLK4 as a mediator of invasion and metastasis in Hela and U2OS cells. However, the function of PLK4 in NB development and progression remains to be elucidated. The study showed the expression level of PLK4 in NB tissues was remarkably upregulated and high expression of PLK4 was negatively correlated with clinical features and survival, which suggested that PLK4 could be a potential tumor-promoting factor of NB. Functional studies indicated downregulation of PLK4 suppressed migration and invasion and promoted apoptosis in NB cells. Further experiments showed that downregulation of PLK4 in NB cells inhibited EMT through the PI3K/Akt signaling pathway. Animal experiments demonstrated that the downregulation of PLK4 in SK-N-BE(2) cells dramatically suppressed tumorigenesis and metastasis. PLK4 may be a promising therapeutic target for NB.
神经母细胞瘤（NB）是婴儿期最常见的恶性肿瘤，也是儿童期最常见的颅外实体瘤。随着诊断和治疗的提高，低危和中危 NB 患者的生存率可达 90%。相比之下，高危 NB 的长期生存率仍<40%，这是因为该肿瘤存在异质性。NB 的发病机制尚不清楚，因此探索 NB 肿瘤发生的机制并发现新的治疗靶点具有重要意义。Polo 样激酶 4（PLK4）是 Polo 样激酶家族的成员之一，是中心体复制的重要调节因子。PLK4 的异常表达在几种癌症中被发现，最近的一项研究揭示了 PLK4 作为 Hela 和 U2OS 细胞侵袭和转移的介质的新功能。然而，PLK4 在 NB 发展和进展中的作用仍有待阐明。研究表明，NB 组织中 PLK4 的表达水平显著上调，PLK4 的高表达与临床特征和生存呈负相关，这表明 PLK4 可能是 NB 的潜在肿瘤促进因子。功能研究表明，下调 PLK4 抑制了 NB 细胞的迁移和侵袭，并促进了细胞凋亡。进一步的实验表明，下调 NB 细胞中的 PLK4 通过 PI3K/Akt 信号通路抑制 EMT。动物实验表明，下调 SK-N-BE(2)细胞中的 PLK4 可显著抑制肿瘤发生和转移。PLK4 可能是 NB 的一个有前途的治疗靶点。
