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Article

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

1
Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia
2
Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
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Department of Pathology and Cytology, University Hospital Dubrava, 10000 Zagreb, Croatia
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Department of Maxillofacial Surgery, University Hospital Dubrava, 10000 Zagreb, Croatia
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Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Carlos S. Moreno
Cancers 2021, 13(17), 4461; https://doi.org/10.3390/cancers13174461
Received: 26 July 2021 / Revised: 25 August 2021 / Accepted: 27 August 2021 / Published: 4 September 2021
(This article belongs to the Collection Cancer Biomarkers)
The process of HPV-mediated oncogenesis in HNSCCs is not fully understood. DLG1 and SCRIB protein expression levels and localization changes were evaluated in a number of HPV16-positive and HPV-negative OPSCCs and seem to be associated with malignant transformation. Moreover, loss of SCRIB expression inversely correlates with higher grade tumors, and this is much more evident in the presence of HPV16 E6. This could serve as a potential marker in predicting development of OPSCCs.
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. View Full-Text
Keywords: HNSCC; OPSCC; HPV; E6; p16; DLG1; SCRIB HNSCC; OPSCC; HPV; E6; p16; DLG1; SCRIB
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MDPI and ACS Style

Lulić, L.; Jakovčević, A.; Manojlović, L.; Dediol, E.; Banks, L.; Tomaić, V. Human DLG1 and SCRIB Are Distinctly Regulated Independently of HPV-16 during the Progression of Oropharyngeal Squamous Cell Carcinomas: A Preliminary Analysis. Cancers 2021, 13, 4461. https://doi.org/10.3390/cancers13174461

AMA Style

Lulić L, Jakovčević A, Manojlović L, Dediol E, Banks L, Tomaić V. Human DLG1 and SCRIB Are Distinctly Regulated Independently of HPV-16 during the Progression of Oropharyngeal Squamous Cell Carcinomas: A Preliminary Analysis. Cancers. 2021; 13(17):4461. https://doi.org/10.3390/cancers13174461

Chicago/Turabian Style

Lulić, Lucija, Antonia Jakovčević, Luka Manojlović, Emil Dediol, Lawrence Banks, and Vjekoslav Tomaić. 2021. "Human DLG1 and SCRIB Are Distinctly Regulated Independently of HPV-16 during the Progression of Oropharyngeal Squamous Cell Carcinomas: A Preliminary Analysis" Cancers 13, no. 17: 4461. https://doi.org/10.3390/cancers13174461

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