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.
Loss of primary cilia is frequently observed in tumor cells. This study shows that histone deacetylase 2 (HDAC2) contributes to the suppression of primary cilia formation in pancreatic ductal adenocarcinoma (PDAC) cells by controlling Aurora A levels in a Kras‐independent manner.
Inhibition or depletion of HDAC2 induces primary ciliogenesis in PDAC cells.
HDAC2 positively regulates expression of Aurora A kinase.
HDAC2 and Kras independently control loss of primary cilia in PDAC cells.
EMBO Reports (2017) 18: 334–343
- Received December 15, 2015.
- Revision received November 22, 2016.
- Accepted December 5, 2016.
- © 2016 The Authors
Subscribers, please sign in with your username and password.