High Enhancer Activity is an Epigenetic Feature of HPV Negative Atypical Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with significant morbidity and mortality and frequent recurrence. Pre-NGS efforts to transcriptionally classify HNSCC into groups of varying prognosis have identified four accepted molecular subtypes of disease: Atypical (AT), Basal (BA), Classical (CL), and Mesenchymal (MS). Here, we investigated the active enhancer landscapes of these subtypes using representative HNSCC cell lines and identified samples belonging to the AT subtype as having increased enhancer activity compared to the other 3 HNSCC subtypes. Cell lines belonging to atypical subtype were more resistant to bromodomain inhibitors (BETi). PRO-Seq experiments that both TCGA tumors and AT cell lines showed higher eRNA transcripts for enhancers controlling BETi resistance pathways, such as lipid metabolism and MAPK signaling. Additionally, HiChIP experiments suggested higher enhancer-promoter (E-P) contacts in the AT subtype, including on genes identified in the eRNA analysis. Consistently, known BETi resistance pathways were upregulated upon exposure to these inhibitors. Together, our results identify that the AT subtype of HNSCC is associated with high enhancer activity, resistance to BET inhibition, and signaling pathways that could serve as future targets for sensitizing HNSCC to BET inhibition.

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THE COMPARISON OF THE EFFECTS OF PANOBINOSTAT AND PKF118-310 ON β-CATENIN-DEPENDENT TRANSCRIPTION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA CELL LINES

Acta Poloniae Pharmaceutica - Drug Research ◽

10.32383/appdr/114081 ◽

2020 ◽

Vol 77 (1) ◽

pp. 77-88 ◽

Cited By ~ 1

Author(s):

Jarosław Paluszczak ◽

Robert Kleszcz ◽

Olga Witczak ◽

Violetta Krajka-Kuźniak

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Carcinoma Cell ◽

Neck Squamous Cell Carcinoma ◽

Squamous Cell Carcinoma Cell ◽

Carcinoma Cell Lines

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Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13123038 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3038

Author(s):

Mickaël Burgy ◽

Aude Jehl ◽

Ombline Conrad ◽

Sophie Foppolo ◽

Véronique Bruban ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Cell Cycle Progression ◽

Locally Advanced ◽

Treatment Resistance ◽

Neck Squamous Cell Carcinoma ◽

Hnscc Cell

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.

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Differences in Extracellular Vesicle Protein Cargo Are Dependent on Head and Neck Squamous Cell Carcinoma Cell of Origin and Human Papillomavirus Status

Cancers ◽

10.3390/cancers13153714 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3714

Author(s):

Christine Goudsmit ◽

Felipe da Veiga Leprevost ◽

Venkatesha Basrur ◽

Lila Peters ◽

Alexey Nesvizhskii ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Extracellular Vesicle ◽

Neck Squamous Cell Carcinoma ◽

Cytokeratin 19 ◽

Oral Keratinocytes ◽

Transformed Cell Lines

To identify potential extracellular vesicle (EV) biomarkers in head and neck squamous cell carcinoma (HNSCC), we evaluated EV protein cargo and whole cell lysates (WCL) from HPV-positive and -negative HNSCC cell lines, as well as normal oral keratinocytes and HPV16-transformed cells. EVs were isolated from serum-depleted, conditioned cell culture media by polyethylene glycol (PEG) precipitation/ultracentrifugation. EV and WCL preparations were analyzed by LC-MS/MS. Candidate proteins detected at significantly higher levels in EV compared with WCL, or compared with EV from normal oral keratinocytes, were identified and confirmed by Wes Simple Western protein analysis. Our findings suggest that these proteins may be potential HNSCC EV markers as proteins that may be (1) selectively included in EV cargo for export from the cell as a strategy for metastasis, tumor cell survival, or modification of tumor microenvironment, or (2) representative of originating cell composition, which may be developed for diagnostic or prognostic use in clinical liquid biopsy applications. This work demonstrates that our method can be used to reliably detect EV proteins from HNSCC, normal keratinocyte, and transformed cell lines. Furthermore, this work has identified HNSCC EV protein candidates for continued evaluation, specifically tenascin-C, HLA-A, E-cadherin, EGFR, EPHA2, and cytokeratin 19.

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Kaempferol Induces Cell Death and Sensitizes Human Head and Neck Squamous Cell Carcinoma Cell Lines to Cisplatin

10.1007/5584_2020_603 ◽

2020 ◽

Author(s):

Mabel Catalán ◽

Catalina Rodríguez ◽

Ivonne Olmedo ◽

Javiera Carrasco-Rojas ◽

Diego Rojas ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Death ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Carcinoma Cell ◽

Human Head ◽

Neck Squamous Cell Carcinoma ◽

Carcinoma Cell Lines

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YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma

Cells ◽

10.3390/cells9051281 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1281 ◽

Cited By ~ 3

Author(s):

Kacper Guglas ◽

Tomasz Kolenda ◽

Maciej Stasiak ◽

Magda Kopczyńska ◽

Anna Teresiak ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Gene Set Enrichment Analysis ◽

Neck Squamous Cell Carcinoma ◽

High Expression ◽

Ribonucleoprotein Particle ◽

Hnscc Cell

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.

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Head and neck squamous cell carcinoma cell lines express mRNA but not protein product for IL-10 and IL-12

Otolaryngology ◽

10.1016/s0194-5998(97)80407-x ◽

1997 ◽

Vol 117 (2) ◽

pp. P189-P189

Author(s):

S GOLDMAN ◽

J MYERS ◽

M LOTTE

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Carcinoma Cell ◽

Protein Product ◽

Neck Squamous Cell Carcinoma ◽

Squamous Cell Carcinoma Cell ◽

Carcinoma Cell Lines

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A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/srep36132 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Aneesha Radhakrishnan ◽

Vishalakshi Nanjappa ◽

Remya Raja ◽

Gajanan Sathe ◽

Vinuth N. Puttamallesh ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Signaling Pathways ◽

Cell Lines ◽

Squamous Cell ◽

Therapeutic Target ◽

Neck Squamous Cell Carcinoma ◽

Dual Specificity ◽

Hnscc Cell

Abstract Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.

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