Minaei, Elahe; Mueller, Simon A; Ashford, Bruce; Thind, Amarinder Singh; Mitchell, Jenny; Perry, Jay R; Genenger, Benjamin; Clark, Jonathan R; Gupta, Ruta; Ranson, Marie (2022). Cancer Progression Gene Expression Profiling Identifies the Urokinase Plasminogen Activator Receptor as a Biomarker of Metastasis in Cutaneous Squamous Cell Carcinoma. Frontiers in oncology, 12, p. 835929. Frontiers Research Foundation 10.3389/fonc.2022.835929
|
Text
fonc-12-835929.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (10MB) | Preview |
Cutaneous squamous cell carcinoma (cSCC) of the head and neck region is the second most prevalent skin cancer, with metastases to regional lymph nodes occurring in 2%-5% of cases. To further our understanding of the molecular events characterizing cSCC invasion and metastasis, we conducted targeted cancer progression gene expression and pathway analysis in non-metastasizing (PRI-) and metastasizing primary (PRI+) cSCC tumors of the head and neck region, cognate lymph node metastases (MET), and matched sun-exposed skin (SES). The highest differentially expressed genes in metastatic (MET and PRI+) versus non-metastatic tumors (PRI-) and SES included PLAU, PLAUR, MMP1, MMP10, MMP13, ITGA5, VEGFA, and various inflammatory cytokine genes. Pathway enrichment analyses implicated these genes in cellular pathways and functions promoting matrix remodeling, cell survival and migration, and epithelial to mesenchymal transition, which were all significantly activated in metastatic compared to non-metastatic tumors (PRI-) and SES. We validated the overexpression of urokinase plasminogen activator receptor (uPAR, encoded by PLAUR) in an extended patient cohort by demonstrating higher uPAR staining intensity in metastasizing tumors. As pathway analyses identified epidermal growth factor (EGF) as a potential upstream regulator of PLAUR, the effect of EGF on uPAR expression levels and cell motility was functionally validated in human metastatic cSCC cells. In conclusion, we propose that uPAR is an important driver of metastasis in cSCC and represents a potential therapeutic target in this disease.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT) |
UniBE Contributor: |
Müller, Simon Andreas |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2234-943X |
Publisher: |
Frontiers Research Foundation |
Language: |
English |
Submitter: |
Stefan Weder |
Date Deposited: |
11 Jan 2023 18:14 |
Last Modified: |
15 Jan 2023 02:18 |
Publisher DOI: |
10.3389/fonc.2022.835929 |
PubMed ID: |
35480116 |
Uncontrolled Keywords: |
cutaneous squamous cell carcinoma (cSSC) extracellular matrix (ECM) matrix metalloproteinase (MMP) metastasis transcriptomics tumor stroma urokinase plasminogen activator (uPA) urokinase plasminogen activator receptor (uPAR) |
BORIS DOI: |
10.48350/176630 |
URI: |
https://boris.unibe.ch/id/eprint/176630 |
Actions (login required)
 |
Edit item |