2. Academic Validation
  3. YAP/Aurora A-mediated ciliogenesis regulates ionizing radiation-induced senescence via Hedgehog pathway in tumor cells

YAP/Aurora A-mediated ciliogenesis regulates ionizing radiation-induced senescence via Hedgehog pathway in tumor cells

  • Biochim Biophys Acta Mol Basis Dis. 2024 Feb 10;1870(4):167062. doi: 10.1016/j.bbadis.2024.167062.
Wei Ma 1,  Li Wei 2,  Liangliang Jin 3,  Qinglong Ma 4,  Tongshan Zhang 1,  Yanfei Zhao 4,  Junrui Hua 5,  Yanan Zhang 5,  Wenjun Wei 1,  Nan Ding 1,  Jufang Wang 6,  Jinpeng He 7
Affiliations

Affiliations

  • 1 Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 73000, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor & Gansu Provincial Clinical Research Center for Laboratory Medicine, Gansu Provincial Hospital, Lanzhou 730000, China.
  • 3 Department of Pathology, The 940th Hospital of Joint Logistics Support force of Chinese People's Liberation Army, Lanzhou 730000, China.
  • 4 School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
  • 5 Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 73000, China.
  • 6 Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 73000, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jufangwang@impcas.ac.cn.
  • 7 Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 73000, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: hejp03@impcas.ac.cn.
PMID: 38342416 DOI: 10.1016/j.bbadis.2024.167062
Abstract

Primary cilia are antenna-like organelles that play critical roles in sensing and responding to various signals. Nevertheless, the function of primary cilia in cellular response to ionizing radiation (IR) in tumor cells remains unclear. Here, we show that primary cilia are frequently expressed in tumor cells and tissues. Notably, IR promotes cilia formation and elongation in time- and dose-dependent manners. Mechanistic study shows that the suppression of YAP/Aurora A pathway contributes to IR-induced ciliogenesis, which is diminished by Aurora A overexpression. The ciliated tumor cells undergo senescence but not Apoptosis in response to IR and the abrogation of cilia formation is sufficient to elevate the lethal effect of IR. Furthermore, we show that IR-induced ciliogenesis leads to the activation of Hedgehog signaling pathway to drive senescence and resist Apoptosis, and its blockage enhances cellular radiosensitivity by switching senescence to Apoptosis. In summary, this work shows evidence of primary cilia in coordinating cellular response to IR in tumor cells, which may help to supply a novel sensitizing target to improve the outcome of radiotherapy.

Keywords

Aurora A; Hedgehog; Ionizing radiation; Primary cilia; Senescence.

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