Radiation-induced IL-1β expression and secretion promote cancer cell migration/invasion via activation of the NF-κB–RIP1 pathway

A. Ram Kang, Jeong Hyun Cho, Na Gyeong Lee, Jin Hee Kwon, Jie Young Song, Sang Gu Hwang, In Su Jung, Jae Sung Kim, Hong Duck Um, Sang Cheul Oh, Jong Kuk Park

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)973-979
Number of pages7
JournalBiochemical and biophysical research communications
Publication statusPublished - 2021 Jan 1

Bibliographical note

Funding Information:
This research was supported by the grant of the Korea Institute of Radiologicak and Medical Sciences(KIRAMS) , funded by the Ministry of Science, ICT ( 505312020 and 505382020 ), and by the Basic Science Research Program through the NRF ( NRF-2018R1D1A1A02047928 and 2020M2D9A2094153 ).

Publisher Copyright:
© 2020 Elsevier Inc.


  • IL-1β
  • Invasion
  • NF-κB
  • RIP1
  • γ-ionizing radiation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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