TY - JOUR
T1 - Comparative gene expression profiling of tobacco-associated HPV-positive versus negative oral squamous carcinoma cell lines
AU - Lepore, Silvia
AU - Lettini, Giacomo
AU - Condelli, Valentina
AU - Sisinni, Lorenza
AU - Piscazzi, Annamaria
AU - Simeon, Vittorio
AU - Zoppoli, Pietro
AU - Pedicillo, Maria Carmela
AU - Natalicchio, Maria Iole
AU - Pietrafesa, Michele
AU - Landriscina, Matteo
N1 - Funding Information:
This work was supported by AIRC Grant IG2015 Id. 16738 to ML.
Publisher Copyright:
© The author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection. Methods: HPV-negative UPCI-SCC-131 and HPV16-positive UPCI-SCC-154 cell lines were compared by whole genome gene expression profiling and subsequently studied for activation of Wnt/βCatenin signaling pathway by the expression of several Wnt-target genes, βCatenin intracellular localization, stem cell features and miRNA let-7e. Gene expression data were validated in head and neck squamous cell carcinoma (HNSCC) public datasets. Results: Gene expression analysis identified Wnt/βCatenin pathway as the unique signaling pathway more active in HPV-negative compared to HPV-positive OSCC cells and this observation was confirmed upon evaluation of several Wnt-target genes (i.e., Cyclin D1, Cdh1, Cdkn2a, Cd44, Axin2, c-Myc and Tcf1). Interestingly, HPV-negative OSCC cells showed higher levels of total βCatenin and its active form, increase of its nuclear accumulation and more prominent stem cell traits. Furthermore, miRNA let-7e was identified as potential upstream regulator responsible for the downregulation of Wnt/βCatenin signaling cascade since its silencing in UPCI-SCC-154 cell resulted in upregulation of Wnt-target genes. Finally, the analysis of two independent gene expression public datasets of human HNSCC cell lines and tumors confirmed that Wnt/βCatenin pathway is more active in HPV-negative compared to HPV-positive tumors derived from individuals with smoking habit. Conclusions: These data suggest that lack of HPV infection is associated with more prominent activation of Wnt/βCatenin signaling pathway and gain of stem-like traits in tobacco-related OSCCs.
AB - Background: HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection. Methods: HPV-negative UPCI-SCC-131 and HPV16-positive UPCI-SCC-154 cell lines were compared by whole genome gene expression profiling and subsequently studied for activation of Wnt/βCatenin signaling pathway by the expression of several Wnt-target genes, βCatenin intracellular localization, stem cell features and miRNA let-7e. Gene expression data were validated in head and neck squamous cell carcinoma (HNSCC) public datasets. Results: Gene expression analysis identified Wnt/βCatenin pathway as the unique signaling pathway more active in HPV-negative compared to HPV-positive OSCC cells and this observation was confirmed upon evaluation of several Wnt-target genes (i.e., Cyclin D1, Cdh1, Cdkn2a, Cd44, Axin2, c-Myc and Tcf1). Interestingly, HPV-negative OSCC cells showed higher levels of total βCatenin and its active form, increase of its nuclear accumulation and more prominent stem cell traits. Furthermore, miRNA let-7e was identified as potential upstream regulator responsible for the downregulation of Wnt/βCatenin signaling cascade since its silencing in UPCI-SCC-154 cell resulted in upregulation of Wnt-target genes. Finally, the analysis of two independent gene expression public datasets of human HNSCC cell lines and tumors confirmed that Wnt/βCatenin pathway is more active in HPV-negative compared to HPV-positive tumors derived from individuals with smoking habit. Conclusions: These data suggest that lack of HPV infection is associated with more prominent activation of Wnt/βCatenin signaling pathway and gain of stem-like traits in tobacco-related OSCCs.
KW - Oral squamous carcinoma
KW - Stemness
KW - Tobacco
KW - Wnt/βCatenin pathway
UR - http://www.scopus.com/inward/record.url?scp=85077470357&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077470357&partnerID=8YFLogxK
U2 - 10.7150/ijms.35133
DO - 10.7150/ijms.35133
M3 - Article
C2 - 31929745
AN - SCOPUS:85077470357
VL - 17
SP - 112
EP - 124
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
SN - 1449-1907
IS - 1
ER -