The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma
Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/M...
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doaj-cade972cde004f18919cf02eb044ef0e2020-11-25T00:30:22ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-01-0121247110.3390/ijms21020471ijms21020471The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell CarcinomaVerena Boschert0Nicola Klenk1Alexander Abt2Sudha Janaki Raman3Markus Fischer4Roman C. Brands5Axel Seher6Christian Linz7Urs D. A. Müller-Richter8Thorsten Bischler9Stefan Hartmann10Department of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Biochemistry and Molecular Biology, Theodor Boveri Institute, Biocenter, University of Würzburg, D-97074 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyCore Unit Systems Medicine, University of Würzburg, D-97080 Würzburg, GermanyDepartment of Oral and Maxillofacial Plastic Surgery, University Hospital Würzburg, D-97070 Würzburg, GermanyHead and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met<sup>high</sup>-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.https://www.mdpi.com/1422-0067/21/2/471hnscchead and neck cancerhgfmetcancer metabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Verena Boschert Nicola Klenk Alexander Abt Sudha Janaki Raman Markus Fischer Roman C. Brands Axel Seher Christian Linz Urs D. A. Müller-Richter Thorsten Bischler Stefan Hartmann |
spellingShingle |
Verena Boschert Nicola Klenk Alexander Abt Sudha Janaki Raman Markus Fischer Roman C. Brands Axel Seher Christian Linz Urs D. A. Müller-Richter Thorsten Bischler Stefan Hartmann The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma International Journal of Molecular Sciences hnscc head and neck cancer hgf met cancer metabolism |
author_facet |
Verena Boschert Nicola Klenk Alexander Abt Sudha Janaki Raman Markus Fischer Roman C. Brands Axel Seher Christian Linz Urs D. A. Müller-Richter Thorsten Bischler Stefan Hartmann |
author_sort |
Verena Boschert |
title |
The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma |
title_short |
The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma |
title_full |
The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma |
title_fullStr |
The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma |
title_full_unstemmed |
The Influence of Met Receptor Level on HGF-Induced Glycolytic Reprogramming in Head and Neck Squamous Cell Carcinoma |
title_sort |
influence of met receptor level on hgf-induced glycolytic reprogramming in head and neck squamous cell carcinoma |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-01-01 |
description |
Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met<sup>high</sup>-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC. |
topic |
hnscc head and neck cancer hgf met cancer metabolism |
url |
https://www.mdpi.com/1422-0067/21/2/471 |
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