354 0

Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor

Title
Radiation promotes invasiveness of non-small-cell lung cancer cells through granulocyte-colony-stimulating factor
Author
이수재
Keywords
EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; FACTOR G-CSF; SIGNALING PATHWAY; GM-CSF; FEEDBACK LOOP; BETA-CATENIN; METASTASIS; ACTIVATION; CARCINOMA
Issue Date
2015-10
Publisher
NATURE PUBLISHING GROUP
Citation
ONCOGENE, v. 34, NO 42, Page. 5372-5382
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.
URI
http://www.nature.com/onc/journal/v34/n42/full/onc2014466a.html?foxtrotcallback=truehttp://hdl.handle.net/20.500.11754/28163
ISSN
0950-9232; 1476-5594
DOI
10.1038/onc.2014.466
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE