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Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop
Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β (TGF-β) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer G...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538541/ https://www.ncbi.nlm.nih.gov/pubmed/34681812 http://dx.doi.org/10.3390/ijms222011151 |
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author | Jin, Yanli Jung, Seung-Nam Lim, Mi Ae Oh, Chan Piao, Yudan Kim, Hae Jong Liu, Lihua Kang, Yea Eun Chang, Jae Won Won, Ho-Ryun Song, Kunho Koo, Bon Seok |
author_facet | Jin, Yanli Jung, Seung-Nam Lim, Mi Ae Oh, Chan Piao, Yudan Kim, Hae Jong Liu, Lihua Kang, Yea Eun Chang, Jae Won Won, Ho-Ryun Song, Kunho Koo, Bon Seok |
author_sort | Jin, Yanli |
collection | PubMed |
description | Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β (TGF-β) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer Genome Atlas (TCGA) data show that the expression of GDF15 is significantly associated with tumor AJCC stage, lymph vascular invasion and tumor grade in HNC. In this study, we confirmed that knockdown of GDF15 attenuated: cell proliferation, migration and invasion via regulation of EMT through a canonical pathway; SMAD2/3 and noncanonical pathways; PI3K/AKT and MEK/ERK in HNC cell lines. Furthermore, we found that early growth response 1 (EGR1) was a transcription factor of GDF15. Interestingly, we also demonstrated that GDF15 could regulate the expression of EGR1, which meant a positive feedback loop occurred between these two factors. Moreover, combined inhibition of both GDF15 and EGR1 in a HNC mouse xenograft model showed significantly decreased tumor volume compared to inhibition of EGR1 or GDF15 alone. Our study showed that the GDF15–EGR1 signaling axis may be a good target in HNC patients. |
format | Online Article Text |
id | pubmed-8538541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85385412021-10-24 Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop Jin, Yanli Jung, Seung-Nam Lim, Mi Ae Oh, Chan Piao, Yudan Kim, Hae Jong Liu, Lihua Kang, Yea Eun Chang, Jae Won Won, Ho-Ryun Song, Kunho Koo, Bon Seok Int J Mol Sci Article Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β (TGF-β) superfamily, has been reported to be overexpressed in different kinds of cancer types. However, the function and mechanism of GDF15 in head and neck cancer (HNC) remains unclear. The Cancer Genome Atlas (TCGA) data show that the expression of GDF15 is significantly associated with tumor AJCC stage, lymph vascular invasion and tumor grade in HNC. In this study, we confirmed that knockdown of GDF15 attenuated: cell proliferation, migration and invasion via regulation of EMT through a canonical pathway; SMAD2/3 and noncanonical pathways; PI3K/AKT and MEK/ERK in HNC cell lines. Furthermore, we found that early growth response 1 (EGR1) was a transcription factor of GDF15. Interestingly, we also demonstrated that GDF15 could regulate the expression of EGR1, which meant a positive feedback loop occurred between these two factors. Moreover, combined inhibition of both GDF15 and EGR1 in a HNC mouse xenograft model showed significantly decreased tumor volume compared to inhibition of EGR1 or GDF15 alone. Our study showed that the GDF15–EGR1 signaling axis may be a good target in HNC patients. MDPI 2021-10-15 /pmc/articles/PMC8538541/ /pubmed/34681812 http://dx.doi.org/10.3390/ijms222011151 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jin, Yanli Jung, Seung-Nam Lim, Mi Ae Oh, Chan Piao, Yudan Kim, Hae Jong Liu, Lihua Kang, Yea Eun Chang, Jae Won Won, Ho-Ryun Song, Kunho Koo, Bon Seok Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop |
title | Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop |
title_full | Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop |
title_fullStr | Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop |
title_full_unstemmed | Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop |
title_short | Transcriptional Regulation of GDF15 by EGR1 Promotes Head and Neck Cancer Progression through a Positive Feedback Loop |
title_sort | transcriptional regulation of gdf15 by egr1 promotes head and neck cancer progression through a positive feedback loop |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538541/ https://www.ncbi.nlm.nih.gov/pubmed/34681812 http://dx.doi.org/10.3390/ijms222011151 |
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