Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-7246
Authors: | Gül, Désirée Schweitzer, Andrea Khamis, Aya Knauer, Shirley K. Ding, Guo-Bin Freudelsperger, Laura Karampinis, Ioannis Strieth, Sebastian Hagemann, Jan Stauber, Roland H. |
Title: | Impact of secretion-active osteoblast-specific factor 2 in promoting progression and metastasis of head and neck cancer |
Online publication date: | 13-Jan-2023 |
Year of first publication: | 2022 |
Language: | english |
Abstract: | Treatment success of head and neck cancer (HNC) is still hampered by tumor relapse due to metastases. Our study aimed to identify biomarkers by exploiting transcriptomics profiles of patient-matched metastases, primary tumors, and normal tissue mucosa as well as the TCGA HNC cohort data sets. Analyses identified osteoblast-specific factor 2 (OSF-2) as significantly overexpressed in lymph node metastases and primary tumors compared to normal tissue. High OSF-2 levels correlate with metastatic disease and reduced overall survival of predominantly HPV-negative HNC patients. No significant correlation was observed with tumor localization or therapy response. These findings were supported by the fact that OSF-2 expression was not elevated in cisplatin-resistant HNC cell lines. OSF-2 was strongly expressed in tumor-associated fibroblasts, suggesting a tumor microenvironment-promoting function. Molecular cloning and expression studies of OSF-2 variants from patients identified an evolutionary conserved bona fide protein secretion signal (1MIPFLPMFSLLLLLIVNPINA21). OSF-2 enhanced cell migration and cellular survival under stress conditions, which could be mimicked by the extracellular administration of recombinant protein. Here, OSF-2 executes its functions via ß1 integrin, resulting in the phosphorylation of PI3K and activation of the Akt/PKB signaling pathway. Collectively, we suggest OSF-2 as a potential prognostic biomarker and drug target, promoting metastases by supporting the tumor microenvironment and lymph node metastases survival rather than by enhancing primary tumor proliferation or therapy resistance. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-7246 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Cancers 14 9 |
Pages or article number: | 2337 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2022 |
ISSN: | 2072-6694 |
Publisher DOI: | 10.3390/cancers14092337 |
Appears in collections: | DFG-491381577-G |
Files in This Item:
File | Description | Size | Format | ||
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![]() | impact_of_secretionactive_ost-20220628120528999.pdf | 6.44 MB | Adobe PDF | View/Open |