Γ-Ionizing radiation-induced activation of the EGFR-p38/ERK-STAT3/CREB-1-EMT pathway promotes the migration/invasion of non-small cell lung cancer cells and is inhibited by podophyllotoxin acetate.
Tumour Biol
; 37(6): 7315-25, 2016 Jun.
Article
em En
| MEDLINE
| ID: mdl-26671552
ABSTRACT
Here, we report a new intracellular signaling pathway involved in γ-ionizing radiation (IR)-induced migration/invasion and show that podophyllotoxin acetate (PA) inhibits the IR-induced invasion and migration of A549 cells (a non-small cell lung cancer (NSCLC) cell line). Our results revealed that IR increased the invasion/migration of A549 cells, and this effect was decreased by 10 nM PA treatment. PA also inhibited the expressions/activities of matrix metalloprotase (MMP) -2, MMP-9, and vimentin, suggesting that PA could block the IR-induced epithelial-mesenchymal transition (EMT). The IR-induced increases in invasion/migration were associated with the activation of EGFR-AKT, and PA inhibited this effect. P38 and p44/42 ERK were also involved in IR-induced invasion/migration, and combined treatments with PA plus inhibitors of each MAPK synergistically blocked this invasion/migration. In terms of transcription factors (TFs), IR-induced increases in cyclic AMP response element-binding protein-1 (CREB-1) and signal transducer and activator of transcription 3 (STAT3) increased invasion/migration and EMT. PA also inhibited these transcription factors and then blocked IR-induced invasion/migration. Collectively, these results indicate that IR induces cancer cell invasion/migration by activating the EGFR-p38/ERK-CREB-1/STAT3-EMT pathway and that PA blocks this pathway to inhibit IR-induced invasion/migration.
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Base de dados:
MEDLINE
Assunto principal:
Podofilotoxina
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Transdução de Sinais
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Carcinoma Pulmonar de Células não Pequenas
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Peptídeos e Proteínas de Sinalização Intracelular
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Transição Epitelial-Mesenquimal
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Raios gama
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Neoplasias Pulmonares
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Proteínas de Neoplasias
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Revista:
Tumour Biol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article