Kobayashi Tetsuo, Nakazono Kosuke, Tokuda Mio, Mashima Yu, Dynlacht Brian David, Itoh Hiroshi
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
EMBO Rep. 2017 Feb;18(2):334-343. doi: 10.15252/embr.201541922. Epub 2016 Dec 27.
Loss of primary cilia is frequently observed in tumor cells, including pancreatic ductal adenocarcinoma (PDAC) cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction and the inability to exit the cell cycle. However, the molecular mechanisms that explain how PDAC cells lose primary cilia are still ambiguous. In this study, we found that inhibition or silencing of histone deacetylase 2 (HDAC2) restores primary cilia formation in PDAC cells. Inactivation of HDAC2 results in decreased Aurora A expression, which promotes disassembly of primary cilia. We further showed that HDAC2 controls ciliogenesis independently of Kras, which facilitates Aurora A expression. These studies suggest that HDAC2 is a novel regulator of primary cilium formation in PDAC cells.
在肿瘤细胞中，包括胰腺导管腺癌（PDAC）细胞，经常观察到初级纤毛的缺失，这表明这种细胞器的缺失可能通过异常信号转导和无法退出细胞周期来促进肿瘤发生。然而，解释PDAC细胞如何失去初级纤毛的分子机制仍然不明确。在本研究中，我们发现抑制或沉默组蛋白去乙酰化酶2（HDAC2）可恢复PDAC细胞中初级纤毛的形成。HDAC2的失活导致极光激酶A（Aurora A）表达降低，从而促进初级纤毛的解体。我们进一步表明，HDAC2独立于促进Aurora A表达的Kras来控制纤毛发生。这些研究表明，HDAC2是PDAC细胞中初级纤毛形成的一种新型调节因子。
