Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
EMBO Rep. 2013 Aug;14(8):741-7. doi: 10.1038/embor.2013.80. Epub 2013 Jun 7.
Loss of primary cilia is frequently observed in tumour cells, including glioblastoma cells, and proposed to benefit tumour growth, but a causal link has not been established. Here, we show that CCRK (cell cycle-related kinase) and its substrate ICK (intestinal cell kinase) inhibit ciliogenesis. Depletion of CCRK leads to accumulation of ICK at ciliary tips, altered ciliary transport and inhibition of cell cycle re-entry in NIH3T3 fibroblasts. In glioblastoma cells with deregulated high levels of CCRK, its depletion restores cilia through ICK and an ICK-related kinase MAK, thereby inhibiting glioblastoma cell proliferation. These results indicate that inhibition of ciliogenesis might be a mechanism used by cancer cells to provide a growth advantage.
原发性纤毛缺失在肿瘤细胞中经常观察到，包括神经胶质瘤细胞，并被认为有利于肿瘤生长，但尚未建立因果关系。在这里，我们表明 CCRK（细胞周期相关激酶）及其底物 ICK（肠细胞激酶）抑制纤毛发生。CCRK 的耗竭导致 ICK 在纤毛尖端积累，改变纤毛运输，并抑制 NIH3T3 成纤维细胞中的细胞周期再进入。在 CCRK 失调水平高的神经胶质瘤细胞中，其耗竭通过 ICK 和 ICK 相关激酶 MAK 恢复纤毛，从而抑制神经胶质瘤细胞增殖。这些结果表明，纤毛发生抑制可能是癌细胞提供生长优势的一种机制。
