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  • [Biochem Biophys Res Commun.] Radiation-induced IL-1β expression and secretion promote cancer cell migration/invasion via activation of the NF-κB-RIP1 pathway

    [Biochem Biophys Res Commun.] Radiation-induced IL-1β expression and secretion promote cancer cell migration/invasion via activation of the NF-κB-RIP1 pathway

    KIRAMS / 강아람, 박종국*

  • 출처
    Biochem Biophys Res Commun.
  • 등재일
    2020 Nov 8
  • 저널이슈번호
    S0006-291X(20)31980-X.
  • 내용

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    Abstract
    Here, we demonstrate that interleukin-1β (IL-1β) contributes to the γ-ionizing radiation (IR)-induced increase of migration/invasion in A549 lung cancer cells, and that this occurs via RIP1 upregulation. We initially observed that the protein expression and secreted concentration of IL-1β were increased upon exposure of A549 cells to IR. We then demonstrated that IR-induced IL-1β is located downstream of the NF-κB-RIP1 signaling pathway. Treatments with siRNA and specific pharmaceutical inhibitors of RIP1 and NF-κB suppressed the IR-induced increases in the protein expression and secreted concentration of IL-1β. IL-1Ra, an antagonist of IL-1β, treatment suppressed the IR-induced epithelial-mesenchymal transition (EMT) and IR-induced invasion/migration in vitro. These results suggest that IL-1β could regulate IR-induced EMT. We also found that IR could induce the expression of IL-1β expression in vivo and that of IL-1 receptor (R) I/II in vitro and in vivo. The IR-induced increases in the protein levels of IL-1 RI/II and IL-1β suggest that an autocrine loop between IL-1β and IL-1 RI/II might play important roles in IR-induced EMT and migration/invasion. Based on these collective results, we propose that IR concomitantly activates NF-κB and RIP1 to trigger the NF-κB-RIP1-IL-1β-IL-1RI/II-EMT pathway, ultimately promoting metastasis.

     

     

     

     

    Affiliations

    A-Ram Kang  1 , Jeong Hyun Cho  1 , Na-Gyeong Lee  1 , Jin-Hee Kwon  1 , Jie-Young Song  1 , Sang-Gu Hwang  1 , In Su Jung  2 , Jae-Sung Kim  1 , Hong-Duck Um  1 , Sang Cheul Oh  3 , Jong Kuk Park  4
    1 Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
    2 Medical Accelerator Team, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
    3 Department of Oncology, Korea University Guro Hospital, Seoul, 08308, Republic of Korea.
    4 Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea. Electronic address: jkpark@kirams.re.kr.

  • 키워드
    IL-1β; Invasion; NF-κB; RIP1; γ-ionizing radiation.
  • 연구소개
    기존의 연구를 통해서 방사선에 의해 발현이 증가되는 여러 단백질들을 발굴하였으며 이중 IL-1β 단백질이 방사선 조사시 발현이 증가하여 암세포의 이동과 침윤을 촉진함을 발견하였습니다. 또한 이때 작용하는 신호 전달 기전으로 NF-κB-RIP1-IL-1β-IL-1RI/II-EMT의 새로운 신호 전달 기전을 규명하였습니다. 본 연구로 방사선과 암미세 환경 조절의 이해와 기반 지식 제공에 도움이 되어드렸으면 합니다
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