Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer

Hyperactivation of the epidermal growth factor receptor (EGFR) pathways and chronic inflammation are common characteristics of oral squamous cell carcinoma (OSCC). Previously, we reported that OSCC cells secrete interleukin-1 beta (IL-1β), which promotes the proliferation of the oral premalignant ce...

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Autores principales: Lee, Chia-Huei, Syu, Shih-Han, Liu, Ko-Jiunn, Chu, Pei-Yi, Yang, Wen-Chan, Lin, Pinpin, Shieh, Wan-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770743/
https://www.ncbi.nlm.nih.gov/pubmed/26462152
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author Lee, Chia-Huei
Syu, Shih-Han
Liu, Ko-Jiunn
Chu, Pei-Yi
Yang, Wen-Chan
Lin, Pinpin
Shieh, Wan-Yu
author_facet Lee, Chia-Huei
Syu, Shih-Han
Liu, Ko-Jiunn
Chu, Pei-Yi
Yang, Wen-Chan
Lin, Pinpin
Shieh, Wan-Yu
author_sort Lee, Chia-Huei
collection PubMed
description Hyperactivation of the epidermal growth factor receptor (EGFR) pathways and chronic inflammation are common characteristics of oral squamous cell carcinoma (OSCC). Previously, we reported that OSCC cells secrete interleukin-1 beta (IL-1β), which promotes the proliferation of the oral premalignant cell line, DOK, and stimulates DOK and OSCC cells to produce the chemokine CXCL1. CXCL1 functions through CXCR2, a G protein-coupled receptor that transactivates EGFR in ovarian and lung cancers. We hypothesized that IL-1β transactivates EGFR through the CXCL1–CXCR2 axis in OSCC. In this study, we demonstrated that tyrosine phosphorylation of EGFR is crucial for the IL-1β-mediated proliferation and subsequent bromodeoxyuridine (BrdU) incorporation of DOK cells because the EGFR inhibitors AG1478 and erlotinib inhibit these abilities in a dose-dependent manner. Addition of IL-1β instantly enhanced CXCL1 expression and secretion (within 15 min) in the DOK and OSCC cell lines. Furthermore, tyrosine phosphorylation of EGFR was significantly enhanced in DOK (1 h) and OSCC (20 min) cell lines after IL-1β treatment, and both cell lines were inhibited on the addition of an IL-1 receptor antagonist (IL-1Ra). CXCL1 treatment resulted in EGFR phosphorylation, whereas the knockdown of CXCL1 expression by lentivirus-mediated shRNA or the addition of the CXCR2 antagonist SB225002 dramatically reduced IL-1β-mediated EGFR phosphorylation and proliferation of DOK cells. Neutralizing antibodies against IL-1β or CXCL1 markedly inhibited the constitutive or IL-1β-induced tyrosine phosphorylation of EGFR in OSCC cells. IL-1β transactivates EGFR through the CXCL1-CXCR2 axis, revealing a novel molecular network in OSCC that is associated with autocrine IL-1β and EGFR signaling.
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spelling pubmed-47707432016-03-21 Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer Lee, Chia-Huei Syu, Shih-Han Liu, Ko-Jiunn Chu, Pei-Yi Yang, Wen-Chan Lin, Pinpin Shieh, Wan-Yu Oncotarget Research Paper Hyperactivation of the epidermal growth factor receptor (EGFR) pathways and chronic inflammation are common characteristics of oral squamous cell carcinoma (OSCC). Previously, we reported that OSCC cells secrete interleukin-1 beta (IL-1β), which promotes the proliferation of the oral premalignant cell line, DOK, and stimulates DOK and OSCC cells to produce the chemokine CXCL1. CXCL1 functions through CXCR2, a G protein-coupled receptor that transactivates EGFR in ovarian and lung cancers. We hypothesized that IL-1β transactivates EGFR through the CXCL1–CXCR2 axis in OSCC. In this study, we demonstrated that tyrosine phosphorylation of EGFR is crucial for the IL-1β-mediated proliferation and subsequent bromodeoxyuridine (BrdU) incorporation of DOK cells because the EGFR inhibitors AG1478 and erlotinib inhibit these abilities in a dose-dependent manner. Addition of IL-1β instantly enhanced CXCL1 expression and secretion (within 15 min) in the DOK and OSCC cell lines. Furthermore, tyrosine phosphorylation of EGFR was significantly enhanced in DOK (1 h) and OSCC (20 min) cell lines after IL-1β treatment, and both cell lines were inhibited on the addition of an IL-1 receptor antagonist (IL-1Ra). CXCL1 treatment resulted in EGFR phosphorylation, whereas the knockdown of CXCL1 expression by lentivirus-mediated shRNA or the addition of the CXCR2 antagonist SB225002 dramatically reduced IL-1β-mediated EGFR phosphorylation and proliferation of DOK cells. Neutralizing antibodies against IL-1β or CXCL1 markedly inhibited the constitutive or IL-1β-induced tyrosine phosphorylation of EGFR in OSCC cells. IL-1β transactivates EGFR through the CXCL1-CXCR2 axis, revealing a novel molecular network in OSCC that is associated with autocrine IL-1β and EGFR signaling. Impact Journals LLC 2015-10-09 /pmc/articles/PMC4770743/ /pubmed/26462152 Text en Copyright: © 2015 Lee et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lee, Chia-Huei
Syu, Shih-Han
Liu, Ko-Jiunn
Chu, Pei-Yi
Yang, Wen-Chan
Lin, Pinpin
Shieh, Wan-Yu
Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
title Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
title_full Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
title_fullStr Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
title_full_unstemmed Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
title_short Interleukin-1 beta transactivates epidermal growth factor receptor via the CXCL1-CXCR2 axis in oral cancer
title_sort interleukin-1 beta transactivates epidermal growth factor receptor via the cxcl1-cxcr2 axis in oral cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770743/
https://www.ncbi.nlm.nih.gov/pubmed/26462152
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