{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gul D"],"funding":["Else-Kröner Fresenius Foundation","Deutsche Forschungsgemeinschaft","Stiftung Tumorforschung Kopf-Hals","DAAD/TransMed"],"pagination":["2337"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9106029"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(9)"],"pubmed_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 <i>TCGA</i> 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 (<sup>1</sup>MIPFLPMFSLLLLLIVNPINA<sup>21</sup>). 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."],"journal":["Cancers"],"pubmed_title":["Impact of Secretion-Active Osteoblast-Specific Factor 2 in Promoting Progression and Metastasis of Head and Neck Cancer."],"pmcid":["PMC9106029"],"funding_grant_id":["TF-OSF","STR 1014; HA8065","ST35","2015_A233"],"pubmed_authors":["Knauer SK","Khamis A","Strieth S","Stauber RH","Freudelsperger L","Schweitzer A","Hagemann J","Karampinis I","Gul D","Ding GB"],"additional_accession":[]},"is_claimable":false,"name":"Impact of Secretion-Active Osteoblast-Specific Factor 2 in Promoting Progression and Metastasis of Head and Neck Cancer.","description":"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 <i>TCGA</i> 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 (<sup>1</sup>MIPFLPMFSLLLLLIVNPINA<sup>21</sup>). 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2025-04-18T21:53:19.454Z","creation":"2025-04-07T09:45:41.927Z"},"accession":"S-EPMC9106029","cross_references":{"pubmed":["35565465"],"doi":["10.3390/cancers14092337"]}}