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The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth
FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that ac...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909991/ https://www.ncbi.nlm.nih.gov/pubmed/36778115 http://dx.doi.org/10.7150/ijbs.74574 |
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author | Lin, Yan Lin, Fengkang Zhang, Zhuoran Peng, Lijia Yang, Wenli Yang, Mao Luo, Bo Wu, Ting Li, Dabing Li, Xuesen Ran, Bing Anuchapreeda, Songyot Chaiwongsa, Rujirek Khamphikham, Pinyaphat Duangmano, Suwit Xu, Jianming He, Tao Pornprasert, Sakorn |
author_facet | Lin, Yan Lin, Fengkang Zhang, Zhuoran Peng, Lijia Yang, Wenli Yang, Mao Luo, Bo Wu, Ting Li, Dabing Li, Xuesen Ran, Bing Anuchapreeda, Songyot Chaiwongsa, Rujirek Khamphikham, Pinyaphat Duangmano, Suwit Xu, Jianming He, Tao Pornprasert, Sakorn |
author_sort | Lin, Yan |
collection | PubMed |
description | FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. Inhibition of MEK or ERK1/2 activities, or knockout of ERK2 but not ERK1 suppressed the FGFR1 signaling-promoted FOXQ1 gene expression. Inhibition of ERK2 in ERK1 knockout cells blocked, while ectopic expression of FOXQ1 in ERK2 knockout cells rescued the FGFR1-signaling-promoted cell growth. Mechanistically, c-FOS, an early response transcription factor upregulated by the FGFR1-MEK-ERK2 pathway, bound to the FOXQ1 promoter to mediate the FGFR1 signaling-promoted FOXQ1 expression. These results indicate that the FGFR1-ERK2-c-FOS-FOXQ1 regulatory axis plays an essential role in the FGFR1 signaling-promoted BC growth. Targeting ERK2 and FOXQ1 should block BC growth caused by a deregulated FGFR1 signaling. |
format | Online Article Text |
id | pubmed-9909991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-99099912023-02-09 The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth Lin, Yan Lin, Fengkang Zhang, Zhuoran Peng, Lijia Yang, Wenli Yang, Mao Luo, Bo Wu, Ting Li, Dabing Li, Xuesen Ran, Bing Anuchapreeda, Songyot Chaiwongsa, Rujirek Khamphikham, Pinyaphat Duangmano, Suwit Xu, Jianming He, Tao Pornprasert, Sakorn Int J Biol Sci Research Paper FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. Inhibition of MEK or ERK1/2 activities, or knockout of ERK2 but not ERK1 suppressed the FGFR1 signaling-promoted FOXQ1 gene expression. Inhibition of ERK2 in ERK1 knockout cells blocked, while ectopic expression of FOXQ1 in ERK2 knockout cells rescued the FGFR1-signaling-promoted cell growth. Mechanistically, c-FOS, an early response transcription factor upregulated by the FGFR1-MEK-ERK2 pathway, bound to the FOXQ1 promoter to mediate the FGFR1 signaling-promoted FOXQ1 expression. These results indicate that the FGFR1-ERK2-c-FOS-FOXQ1 regulatory axis plays an essential role in the FGFR1 signaling-promoted BC growth. Targeting ERK2 and FOXQ1 should block BC growth caused by a deregulated FGFR1 signaling. Ivyspring International Publisher 2023-01-01 /pmc/articles/PMC9909991/ /pubmed/36778115 http://dx.doi.org/10.7150/ijbs.74574 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Lin, Yan Lin, Fengkang Zhang, Zhuoran Peng, Lijia Yang, Wenli Yang, Mao Luo, Bo Wu, Ting Li, Dabing Li, Xuesen Ran, Bing Anuchapreeda, Songyot Chaiwongsa, Rujirek Khamphikham, Pinyaphat Duangmano, Suwit Xu, Jianming He, Tao Pornprasert, Sakorn The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth |
title | The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth |
title_full | The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth |
title_fullStr | The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth |
title_full_unstemmed | The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth |
title_short | The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth |
title_sort | fgfr1 signaling pathway upregulates the oncogenic transcription factor foxq1 to promote breast cancer cell growth |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909991/ https://www.ncbi.nlm.nih.gov/pubmed/36778115 http://dx.doi.org/10.7150/ijbs.74574 |
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