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Cancers
Special Issues
Molecular Mechanisms in Head and Neck Cancer
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Molecular Mechanisms in Head and Neck Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 31 October 2025 | Viewed by 6289

Special Issue Editors

Dr. Désirée Gül

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Guest Editor
Department of Otorhinolaryngology Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, Mainz, Germany
Interests: head and neck tumor oncology; translational oncology; liquid biopsy research
Dr. Jan Hagemann

E-Mail Website
Guest Editor
Department of Otorhinolaryngology Head and Neck Surgery, University Medical Center, Mainz, Germany
Interests: head and neck tumor oncology; clinical research; liquid biopsy
Prof. Dr. Roland Hans Stauber

E-Mail Website
Guest Editor
Department of Otorhinolaryngology Head and Neck Surgery, Molecular and Cellular Oncology, University Medical Center, Mainz, Germany
Interests: translational oncology; nanobiomedicine; chemical biology

Special Issue Information

Dear Colleagues,

Head and neck cancers (HNCs) are among the most common malignant neoplasms in humans. Due to the late disease presentation of the patient, lack of suitable biomarkers, and corresponding drugs for individually targeted therapy approaches, survival rates for HNC patients are still unsatisfying. The key to novel effective therapies, innovative predictive tools, and relevant drug targets is the detailed knowledge of underlying molecular mechanisms in HNCs.

This Special Issue aims to provide new insights into molecular mechanisms, and cellular signaling networks regulating the development, growth, and metastasis of head and neck tumors. This knowledge can provide a new impetus for the development of innovative (multi-targeting) treatment strategies, and thus will aid in improving the prognosis of HNC patients.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: the molecular pathways of head and neck cancer; molecular alterations at genomic, transcriptomic, and proteomic levels; novel methods for biomarker identification; and liquid biopsies in HNC.

We look forward to receiving your contributions.

Dr. Désirée Gül
Dr. Jan Hagemann
Prof. Dr. Roland Hans Stauber
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers 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 2900 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

  • head and neck cancer
  • translational research
  • molecular pathways
  • cellular signaling
  • biomarkers
  • liquid biopsies
  • transcriptome
  • proteome
  • survival

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Published Papers (4 papers)

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Research

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13 pages, 4845 KiB  
Article
PIP4K2B Protein Regulation by NSD1 in HPV-Negative Head and Neck Squamous Cell Carcinoma
by Iuliia Topchu, Igor Bychkov, Ekaterina Roshchina, Petr Makhov and Yanis Boumber
Cancers 2024, 16(6), 1180; https://doi.org/10.3390/cancers16061180 - 17 Mar 2024
Cited by 3 | Viewed by 1475
Abstract
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2 [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) ranks among the most prevalent global cancers. Despite advancements in treatments, the five-year survival rate remains at approximately 66%. The histone methyltransferase NSD1, known for its role in catalyzing histone H3 lysine 36 di-methylation (H3K36me2), emerges as a potential oncogenic factor in HNSCC. Our study, employing Reverse Phase Protein Array (RPPA) analysis and subsequent validation, reveals that PIP4K2B is a key downstream target of NSD1. Notably, PIP4K2B depletion in HNSCC induces downregulation of the mTOR pathway, resulting in diminished cell growth in vitro. Our investigation highlights a direct, positive regulatory role of NSD1 on PIP4K2B gene transcription through an H3K36me2-dependent mechanism. Importantly, the impact of PIP4K2B appears to be context-dependent, with overexpression rescuing cell growth in laryngeal HNSCC cells but not in tongue/hypopharynx cells. In conclusion, our findings implicate PIP4K2B as a novel NSD1-dependent protein in HNSCC, suggesting its potential significance for laryngeal cancer cell survival. This insight contributes to our understanding of the molecular landscape in HNSCC and establishes PIP4KB as a promising target for drug development. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Head and Neck Cancer)
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20 pages, 7739 KiB  
Article
A Novel LncRNA MASCC1 Regulates the Progression and Metastasis of Head and Neck Squamous Cell Carcinoma by Sponging miR-195
by Yujia Wang, Zhen Qin, Yiwen Chen, Yunfei Zheng and Lingfei Jia
Cancers 2023, 15(24), 5792; https://doi.org/10.3390/cancers15245792 - 11 Dec 2023
Cited by 1 | Viewed by 1358
Abstract
The altered expression of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. We performed a high-throughput analysis of lncRNA expression in strictly selected pairs of metastatic head and neck squamous cell carcinoma (HNSCC) and non-metastatic HNSCC samples. We identified a novel lncRNA, [...] Read more.
The altered expression of long noncoding RNAs (lncRNAs) is associated with human carcinogenesis. We performed a high-throughput analysis of lncRNA expression in strictly selected pairs of metastatic head and neck squamous cell carcinoma (HNSCC) and non-metastatic HNSCC samples. We identified a novel lncRNA, which was highly expressed in metastatic HNSCC, named Metastasis Associated Squamous Cell Carcinoma 1 (MASCC1), for further study. Using qRT-PCR, we further compared MASCC1 expression in 60 HNSCC samples. The results show that high expression of MASCC1 in patients with HNSCC was related to poor prognosis. In vitro, MASCC1 knockdown (KD) inhibited HNSCC proliferation, migration, invasion, and tumor sphere formation, while promoting apoptosis. In vivo, MASCC1 KD inhibited HNSCC growth and lymph node metastasis. Mechanistically, MASCC1 acted as a competing endogenous RNA (ceRNA) by binding to miR-195, subsequently regulating the expression of Cyclin D1, BCL-2, and YAP1. Moreover, miR-195 overexpression rescued the effects of MASCC1 on the biological behaviors of HNSCC. Taken together, our results suggest that MASCC1 is a novel oncogene that can predict the prognosis of patients with HNSCC and is a potential therapeutic target for HNSCC intervention. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Head and Neck Cancer)
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13 pages, 3156 KiB  
Article
SOX2-OT Binds with ILF3 to Promote Head and Neck Cancer Progression by Modulating Crosstalk between STAT3 and TGF-β Signaling
by Ru Wang, Yifan Yang, Lingwa Wang, Qian Shi, Hongzhi Ma, Shizhi He, Ling Feng and Jugao Fang
Cancers 2023, 15(24), 5766; https://doi.org/10.3390/cancers15245766 - 8 Dec 2023
Cited by 1 | Viewed by 1308
Abstract
Long non-coding RNA (lncRNA) is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The molecular mechanism of lncRNA SOX2-OT in HNSCC remains unclear. Therefore, we aimed to elucidate the oncogenic role of SOX2-OT in HNSCC. QRT-PCR analysis was performed [...] Read more.
Long non-coding RNA (lncRNA) is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The molecular mechanism of lncRNA SOX2-OT in HNSCC remains unclear. Therefore, we aimed to elucidate the oncogenic role of SOX2-OT in HNSCC. QRT-PCR analysis was performed in 61 pairs of HNSCC cancer tissues, adjacent normal tissues, and 68 plasma samples confirmed that lncRNA SOX2-OT was overexpressed in cancer tissues and plasma samples, which served as a poor prognostic factor for HNSCC. The FISH assay demonstrated that SOX2-OT was localized in the nucleus and cytoplasm of HNSCC cell lines. Further, the cell function assay confirmed that SOX2-OT promoted cell proliferation and metastasis in vitro and in vivo. RNA pulldown and RIP assay results revealed that SOX2-OT bonds with ILF3 in HNSCC, and the rescue assay confirmed that SOX2-OT played an oncogenic role depending on ILF3 protein expression. Ingenuity pathway analysis and Western blotting indicated that SOX2-OT regulated HNSCC progression by promoting STAT3 phosphorylation and modulating the crosstalk between STAT3 and TGF-β signaling. These results reveal evidence for the role of SOX2-OT in HNSCC progression and metastasis by binding to ILF3, which may serve as a therapeutic target and prognostic biomarker in HNSCC. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Head and Neck Cancer)
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Review

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22 pages, 1558 KiB  
Review
Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma
by William R. Britton, Isabel Cioffi, Corinne Stonebraker, Matthew Spence, Ogoegbunam Okolo, Cecilia Martin, Brian Henick, Hiroshi Nakagawa and Anuraag S. Parikh
Cancers 2024, 16(17), 3047; https://doi.org/10.3390/cancers16173047 - 31 Aug 2024
Viewed by 1594
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide according to GLOBOCAN estimates from 2022. Current therapy options for recurrent or metastatic disease are limited to conventional cytotoxic chemotherapy and immunotherapy, with few targeted therapy options readily [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide according to GLOBOCAN estimates from 2022. Current therapy options for recurrent or metastatic disease are limited to conventional cytotoxic chemotherapy and immunotherapy, with few targeted therapy options readily available. Recent single-cell transcriptomic analyses identified TGF-β signaling as an important mediator of functional interplays between cancer-associated fibroblasts and a subset of mesenchymal cancer cells. This signaling was shown to drive invasiveness, treatment resistance, and immune evasion. These data provide renewed interest in the TGF-β pathway as an alternative therapeutic target, prompting a critical review of previous clinical data which suggest a lack of benefit from TGF-β inhibitors. While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Head and Neck Cancer)
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