Human DLG1 and SCRIB Are Distinctly Regulated Independently of HPV-16 during the Progression of Oropharyngeal Squamous Cell Carcinomas: A Preliminary Analysis

Cancers

Antonia Jakovčević¹  Emil Dediol²  Luka Manojlović³  Lucija Lulić⁴  Vjekoslav Tomaić⁴  Lawrence Banks⁵ 

[1]Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, 10000 Zagreb, Croatia

[2]Department of Maxillofacial Surgery, University Hospital Dubrava, 10000 Zagreb, Croatia

[3]Department of Pathology and Cytology, University Hospital Dubrava, 10000 Zagreb, Croatia

[4]Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia

[5]Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy

关键词: HNSCC;    OPSCC;    HPV;    E6;    p16;    DLG1;   

DOI  :  10.3390/cancers13174461

来源: DOAJ

【 摘 要 】

The major causative agents of head and neck squamous cell carcinomas (HNSCCs) are either environmental factors, such as tobacco and alcohol consumption, or infection with oncogenic human papillomaviruses (HPVs). An important aspect of HPV-induced oncogenesis is the targeting by the E6 oncoprotein of PDZ domain-containing substrates for proteasomal destruction. Tumor suppressors DLG1 and SCRIB are two of the principal PDZ domain-containing E6 targets. Both have been shown to play critical roles in the regulation of cell growth and polarity and in maintaining the structural integrity of the epithelia. We investigated how modifications in the cellular localization and protein expression of DLG1 and SCRIB in HPV16-positive and HPV-negative histologic oropharyngeal squamous cell carcinomas (OPSCC) might reflect disease progression. HPV presence was determined by p16 staining and HPV genotyping. Whilst DLG1 expression levels did not differ markedly between HPV-negative and HPV16-positive OPSCCs, it appeared to be relocated from cell–cell contacts to the cytoplasm in most samples, regardless of HPV16 positivity. This indicates that alterations in DLG1 distribution could contribute to malignant progression in OPSCCs. Interestingly, SCRIB was also relocated from cell–cell contacts to the cytoplasm in the tumor samples in comparison with normal tissue, regardless of HPV16 status, but in addition there was an obvious reduction in SCRIB expression in higher grade tumors. Strikingly, loss of SCRIB was even more pronounced in HPV16-positive OPSCCs. These alterations in SCRIB levels may contribute to transformation and loss of tissue architecture in the process of carcinogenesis and could potentially serve as markers in the development of OPSCCs.

【 授权许可】

Unknown