 세미나 시리즈 
건국대학교 생명과학특성학과/대학원 생명과학과
4단계 BK21 미래통합형 생명과학 인재양성 사업단
RIP [Receptor (TNFRSF)-interacting serine-threonine kinase] 1 and its associated cell signaling network
promote EMT and metastasis
We demonstrated that γ-ionizing radiation (IR) triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–
STAT3/CREB-1–EMT pathway. Additionally, we have reported the involvement of a novel intracellular signaling mechanism in γ-
ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon
exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved
in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal
transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration.
Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2,
MMP-9 and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB.
Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression, followed by
a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and
NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis. Next, we also studied 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
연사: 박종국 교수 (한국원자력의학원 방사선의생명연구부)
일시: 2021년 04월 27일 화요일. 오후 5시~6시
 
https://us02web.zoom.us/j/87162544958?pwd=UGVTTlphRmFheW9TNlhRMHFzNWptZz09
회의 ID: 871 6254 4958
암호: 299187