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HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer
CONCLUSIONS: Our results give a clear molecular mechanism at the basis of HPV regulation of the DDR pathway. In particular, we show how HPV stabilizes SMAD4 to promote DDR protein expression, which may be used to facilitate viral replication and HNC onset. Moreover, we found that SMAD4 silencing in HPV-positive HNC cell lines increases sensitivity to cisplatin treatment, suggesting that HPV-positive HNC with low SMAD4 expression may be preferentially susceptible to similar treatments.PMID:35144669 | DOI:10.1186/s13046-022-02258-9
Source: Cell Research - February 11, 2022 Category: Cytology Authors: Simona Citro Claudia Miccolo Alessandro Medda Lavinia Ghiani Marta Tagliabue Mohssen Ansarin Susanna Chiocca Source Type: research

Cancers, Vol. 12, Pages 2963: CTEN Induces Tumour Cell Invasion and Survival and Is Prognostic in Radiotherapy-Treated Head and Neck Cancer
Kim Gareth J. Thomas Head and neck squamous cell carcinoma (HNSCC) is a heterogenous disease treated with surgery and/or (chemo) radiotherapy, but up to 50% of patients with late-stage disease develop locoregional recurrence. Determining the mechanisms underpinning treatment resistance could identify new therapeutic targets and aid treatment selection. C-terminal tensin-like (CTEN) is a member of the tensin family, upregulated in several cancers, although its expression and function in HNSCC are unknown. We found that CTEN is commonly upregulated in HNSCC, particularly HPV−ve tumours. In vitro CTEN was...
Source: Cancers - October 13, 2020 Category: Cancer & Oncology Authors: Jason C. Fleming Jeongmin Woo Karwan Moutasim Christopher J. Hanley Steven J. Frampton Oliver Wood Matthew Ward Christopher H Woelk Christian H. Ottensmeier Sassan Hafizi Dae Kim Gareth J. Thomas Tags: Article Source Type: research

Cancers, Vol. 11, Pages 1848: The Potential Impact of Connexin 43 Expression on Bcl-2 Protein Level and Taxane Sensitivity in Head and Neck Cancers –In Vitro Studies
This study aimed to test the role of Cx43 protein on Bcl-2 expression, tumor progression and response to taxane-based treatment in HNSCC. Human papillomavirus (HPV) negative HNSCC cell lines were tested for paclitaxel sensitivity through measuring apoptosis induction, cell viability and changes in Cx43 and Bcl-2 levels using flow cytometry, cell viability assay, immunocytochemistry and western blot. Inhibition of Cx43 expression using siRNA increased Bcl-2 protein levels in SCC25 (tongue squamous cell carcinoma) cells, while forced Cx43 expression reduced Bcl-2 levels and supported paclitaxel cytotoxicity in FaDu (hypophar...
Source: Cancers - November 21, 2019 Category: Cancer & Oncology Authors: Bianka Gurbi Di ána Brauswetter Attila Varga P ál Gyulavári Kinga P énzes J ózsef Murányi Veronika Z ámbó Ede Birtalan Tibor Kren ács David Laurence Becker Mikl ós Csala Istv án Vályi-Nagy Istv án Peták Korn él Dános Tags: Article Source Type: research

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway
In conclusion, the present study elucidated that the activity of SMYD2 in NSCLC may affect the cell sensitivity to chemotherapeutic agents, especially to CDDP. The elevated SMYD2 mediated CDDP resistance and malignant phenotype in NSCLC, indicating that SMYD2 may be a useful biomarker of CDDP resistance in NSCLC. Inhibition of SMYD2 contributes to the methylation-related activation of p53 and thus results in cell apoptosis. Furthermore, combination treatment with CDDP and an SMYD2 inhibitor had a synergistically antitumor effects in a xenograft model in vivo. Given that SMYD2 has reversible effects and is a targetable prot...
Source: Frontiers in Oncology - April 25, 2019 Category: Cancer & Oncology Source Type: research

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective
Conclusion Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - April 15, 2019 Category: Physiology Source Type: research

Human papillomavirus oncogenic E6 protein regulates human β-defensin 3 (hBD3) expression via the tumor suppressor protein p53.
Authors: DasGupta T, Nweze EI, Yue H, Wang L, Jin J, Ghosh SK, Kawsar HI, Zender C, Androphy EJ, Weinberg A, McCormick TS, Jin G Abstract Human β-defensin-3 (hBD3) is an epithelial cell-derived innate immune regulatory molecule overexpressed in oral dysplastic lesions and fosters a tumor-promoting microenvironment. Expression of hBD3 is induced by the epidermal growth factor receptor signaling pathway. Here we describe a novel pathway through which the high-risk human papillomavirus type-16 (HPV-16) oncoprotein E6 induces hBD3 expression in mucosal keratinocytes. Ablation of E6 by siRNA induces the tumor suppresso...
Source: Oncotarget - April 3, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer
Conclusions: These findings demonstrate that the overexpression of miR-363 reduces cellular migration in head and neck cancer and reveal the biological relationship between miR-363, myosin 1b, and HPV-positive SCCHN.
Source: BMC Cancer - November 6, 2015 Category: Cancer & Oncology Authors: Bhavana ChapmanAbigail WaldParvez AkhtarAna MunkoJingjing XuSandra GibsonJennifer GrandisRobert FerrisSaleem Khan Source Type: research

Viruses, Vol. 7, Pages 5243-5256: HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells
Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this ...
Source: Viruses - October 5, 2015 Category: Virology Authors: Peng SunLi DongAlasdair MacDonaldShahrzad AkbariMichael EdwardMalcolm HodginsScott JohnstoneSheila Graham Tags: Article Source Type: research

Abstract 813: Human papillomavirus 16 oncoprotein E6 upregulates c-Met partially through p53 in squamous cell carcinoma of the head and neck
Conclusion: Our results show that c-Met expression is upregulated by HPV E6, which is partially mediated by p53. The data suggest that targeting c-Met may serve as a novel approach for treating HPV-associated OPSCC.(This study was supported by grants from Small Business Innovation Research (SBIR) Program (HHSN261201200097C), National Institutes of Health (R33 CA161873), and National Cancer Institute (NCI P50 CA 128613, Head and Neck SPORE).Citation Format: Guoqing Qian, Dongsheng Wang, Kelly R. Magliocca, Praveen Duggal, Sreenivas Nannapaneni, Sungjin Kim, Zhengjia Chen, Dong M. Shin, Nabil F. Saba, Zhuo G. Chen. Human pap...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Qian, G., Wang, D., Magliocca, K. R., Duggal, P., Nannapaneni, S., Kim, S., Chen, Z., Shin, D. M., Saba, N. F., Chen, Z. G. Tags: Carcinogenesis Source Type: research