Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor
- Authors
- Cui, Y-H; Suh, Y.; Lee, H-J; Yoo, K-C; Uddin, N.; Jeong, Y-J; Lee, J-S; Hwang, S-G; Nam, S-Y; Kim, M-J; Lee, S-J
- Issue Date
- Oct-2015
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- ONCOGENE, v.34, no.42, pp.5372 - 5382
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOGENE
- Volume
- 34
- Number
- 42
- Start Page
- 5372
- End Page
- 5382
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/24846
- DOI
- 10.1038/onc.2014.466
- ISSN
- 0950-9232
- Abstract
- Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by beta-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of beta-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/ signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 서울 자연과학대학 > 서울 생명과학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/24846)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.