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Cells
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New Insights into Head and Neck Squamous Cell Carcinoma
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New Insights into Head and Neck Squamous Cell Carcinoma

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 11084

Special Issue Editors

Dr. Jozsef Dudas

E-Mail Website
Guest Editor
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria
Interests: epithelial-to-mesenchymal transition; fibroblasts; chemokines; head and neck squamous cell carcinoma; curcumin; tumor progression
Special Issues, Collections and Topics in MDPI journals
Dr. Teresa Steinbichler

E-Mail Website
Guest Editor
Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Innsbruck, A-6020 Innsbruck, Austria
Interests: therapy resistance; head and neck surgery; epithelial mesenchymal transition; extracellular vesicles; cancer stem cells

Special Issue Information

Dear Colleagues,

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent malignancies in the world. In the last decades, a significant improvement in the diagnostic, therapeutic management, and patient care of HNSCC has been achieved, but 25 % of the patients with incident HNSCC do not completely respond to first-line therapy, which severely decreases prognosis. Parallel with the reduction of the number of patients with smoking- and alcohol-related HNSCC, the number of patients with human papilloma virus (HPV)-related HNSCC is increasing. HNSCC tumor cells associated with genomic aberrations or with viral infections could be recognized by the host immune system. Nevertheless, an efficient immune response might be hampered by the activation of immune checkpoints. It is difficult to define therapeutically targetable driving gene mutations in HNSCC, and predictive and prognostic biomarkers are also rare. HNSCC is a highly heterogenic cancer entity that might adapt to various therapeutic approaches, and consequently can generate surviving tumor cells after therapy. Moreover, not only the tumor cells themselves, but the whole cancer tissue including the cancer microenvironment might contribute to therapy resistance. HNSCC is a tough target, but approaches, sooner or later, will achieve a tumor-free status for the patients. This Issue is aimed at that purpose, we are keen on reading your reports and will edit a Special Issue for a concise image on HNSCC.

Some topics of interest are the following

  • Therapeutic approaches
  • Molecular targets
  • Metabolism and hypoxia, and their clinical consequences
  • Molecular markers detected non-invasively
  • New insights in clinical management
  • Update in HNSCC pathology
  • Signal transduction and its targetability
  • Tumor microenvironment and epithelial-to-mesenchymal transition
  • Cancer stemness, cell death, autophagy
  • Extracellular vesicules, nanoparticles, and drug delivery
  • microRNAs, non-coding RNAs and their therapeutic use, and oncolytic viruses

 Dr. Teresa Steinbichler
Dr. Jozsef Dudas
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HNSCC grading and staging
  • Personalized therapy
  • Targeted therapy
  • Extracellular vesicles
  • Oncolytic virus
  • Immune checkpoint
  • Cancer stem cells
  • Translational medicine

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Published Papers (3 papers)

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Research

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22 pages, 5646 KiB  
Article
Multifaceted and Intricate Oncogenic Mechanisms of NDRG1 in Head and Neck Cancer Depend on Its C-Terminal 3R-Motif
by Guo-Rung You, Joseph T. Chang, Hsiao-Fan Li and Ann-Joy Cheng
Cells 2022, 11(9), 1581; https://doi.org/10.3390/cells11091581 - 7 May 2022
Cited by 5 | Viewed by 2723
Abstract
N-Myc downstream-regulated 1 (NDRG1) has inconsistent oncogenic functions in various cancers. We surveyed and characterized the role of NDRG1 in head and neck cancer (HNC). Cellular methods included spheroid cell formation, clonogenic survival, cell viability, and Matrigel invasion assays. Molecular techniques included transcriptomic [...] Read more.
N-Myc downstream-regulated 1 (NDRG1) has inconsistent oncogenic functions in various cancers. We surveyed and characterized the role of NDRG1 in head and neck cancer (HNC). Cellular methods included spheroid cell formation, clonogenic survival, cell viability, and Matrigel invasion assays. Molecular techniques included transcriptomic profiling, RT-qPCR, immunoblotting, in vitro phosphorylation, immunofluorescent staining, and confocal microscopy. Prognostic significance was assessed by Kaplan–Meier analysis. NDRG1 participated in diverse oncogenic functions in HNC cells, mainly stress response and cell motility. Notably, NDRG1 contributed to spheroid cell growth, radio-chemoresistance, and upregulation of stemness-related markers (CD44 and Twist1). NDRG1 facilitated cell migration and invasion, and was associated with modulation of the extracellular matrix molecules (fibronectin, vimentin). Characterizing the 3R-motif in NDRG1 revealed its mechanism in the differential regulation of the phenotypes. The 3R-motif displayed minimal effect on cancer stemness but was crucial for cell motility. Phosphorylating the motif by GSK3b at serine residues led to its nuclear translocation to promote motility. Clinical analyses supported the oncogenic function of NDRG1, which was overexpressed in HNC and associated with poor prognosis. The data elucidate the multifaceted and intricate mechanisms of NDRG1 in HNC. NDRG1 may be a prognostic indicator or therapeutic target for refractory HNC. Full article
(This article belongs to the Special Issue New Insights into Head and Neck Squamous Cell Carcinoma)
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23 pages, 9489 KiB  
Article
KLF4, Slug and EMT in Head and Neck Squamous Cell Carcinoma
by Julia Ingruber, Dragana Savic, Teresa Bernadette Steinbichler, Susanne Sprung, Felix Fleischer, Rudolf Glueckert, Gabriele Schweigl, Ira-Ida Skvortsova, Herbert Riechelmann and József Dudás
Cells 2021, 10(3), 539; https://doi.org/10.3390/cells10030539 - 3 Mar 2021
Cited by 18 | Viewed by 3725
Abstract
Epithelial to mesenchymal transition (EMT) is clinically relevant in head and neck squamous cell carcinoma (HNSCC). We hypothesized that EMT-transcription factors (EMT-TFs) and an anti-EMT factor, Krüppel-like-factor-4 (KLF4) regulate EMT in HNSCC. Ten control mucosa and 37 HNSCC tissue samples and three HNSCC [...] Read more.
Epithelial to mesenchymal transition (EMT) is clinically relevant in head and neck squamous cell carcinoma (HNSCC). We hypothesized that EMT-transcription factors (EMT-TFs) and an anti-EMT factor, Krüppel-like-factor-4 (KLF4) regulate EMT in HNSCC. Ten control mucosa and 37 HNSCC tissue samples and three HNSCC cell lines were included for investigation of EMT-TFs, KLF4 and vimentin at mRNA and protein levels. Slug gene expression was significantly higher, whereas, KLF4 gene expression was significantly lower in HNSCC than in normal mucosa. In the majority of HNSCC samples, there was a significant negative correlation between KLF4 and Slug gene expression. Slug gene expression was significantly higher in human papilloma virus (HPV) negative HNSCC, and in tumor samples with irregular p53 gene sequence. Transforming-growth-factor-beta-1 (TGF- β1) contributed to downregulation of KLF4 and upregulation of Slug. Two possible regulatory pathways could be suggested: (1) EMT-factors induced pathway, where TGF-β1 induced Slug together with vimentin, and KLF4 was down regulated at the same time; (2) p53 mutations contributed to upregulation and stabilization of Slug, where also KLF4 could co-exist with EMT-TFs. Full article
(This article belongs to the Special Issue New Insights into Head and Neck Squamous Cell Carcinoma)
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Review

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15 pages, 852 KiB  
Review
The Emerging Significance of Histone Lysine Demethylases as Prognostic Markers and Therapeutic Targets in Head and Neck Cancers
by Dawid Dorna and Jarosław Paluszczak
Cells 2022, 11(6), 1023; https://doi.org/10.3390/cells11061023 - 17 Mar 2022
Cited by 11 | Viewed by 3474
Abstract
Epigenetic aberrations, associated with altered DNA methylation profiles and global changes in the level of histone modifications, are commonly detected in head and neck squamous cell carcinomas (HNSCC). Recently, histone lysine demethylases have been implicated in the pathogenesis of HNSCC and emerged as [...] Read more.
Epigenetic aberrations, associated with altered DNA methylation profiles and global changes in the level of histone modifications, are commonly detected in head and neck squamous cell carcinomas (HNSCC). Recently, histone lysine demethylases have been implicated in the pathogenesis of HNSCC and emerged as potential molecular targets. Histone lysine demethylases (KDMs) catalyze the removal of methyl groups from lysine residues in histones. By affecting the methylation of H3K4, H3K9, H3K27, or H3K36, these enzymes take part in transcriptional regulation, which may result in changes in the level of expression of tumor suppressor genes and protooncogenes. KDMs are involved in many biological processes, including cell cycle control, senescence, DNA damage response, and heterochromatin formation. They are also important regulators of pluripotency. The overexpression of most KDMs has been observed in HNSCC, and their inhibition affects cell proliferation, apoptosis, cell motility, invasiveness, and stemness. Of all KDMs, KDM1, KDM4, KDM5, and KDM6 proteins are currently regarded as the most promising prognostic and therapeutic targets in head and neck cancers. The aim of this review is to present up-to-date knowledge on the significance of histone lysine demethylases in head and neck carcinogenesis and to discuss the possibility of using them as prognostic markers and pharmacological targets in patients’ treatment. Full article
(This article belongs to the Special Issue New Insights into Head and Neck Squamous Cell Carcinoma)
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