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Activation of p53-regulated pro-survival signals and hypoxia-independent mitochondrial targeting of TIGAR by human papillomavirus E6 oncoproteins
Virology. 2023 May 22;585:1-20. doi: 10.1016/j.virol.2023.05.004. Online ahead of print.ABSTRACTThe high-risk subtype human papillomaviruses (hrHPVs) infect and oncogenically transform basal epidermal stem cells associated with the development of squamous-cell epithelial cancers. The viral E6 oncoprotein destabilizes the p53 tumor suppressor, inhibits p53 K120-acetylation by the Tat-interacting protein of 60 kDa (TIP60, or Kat5), and prevents p53-dependent apoptosis. Intriguingly, the p53 gene is infrequently mutated in HPV + cervical cancer clinical isolates which suggests a possible paradoxical role for this gatekeeper i...
Source: Virology - May 31, 2023 Category: Virology Authors: Lacin Yapindi Tetiana Bowley Nick Kurtaneck Rachel L Bergeson Kylie James Jillian Wilbourne Carolyn K Harrod Brenda Y Hernandez Brooke M Emerling Courtney Yates Robert Harrod Source Type: research

Viruses, Vol. 14, Pages 1150: The Process of Filopodia Induction during HPV Infection
In this study, we demonstrate that after HPV16 comes into contact with a plasma membrane receptor, there are cytoskeletal changes resulting in an increase of filopodia numbers. This increase in filopodia numbers was transient and was maintained during the first two hours after virus addition. Our data show that there is a statistically significant increase in infection when filopodia numbers are increased by the addition of drug and virus simultaneously, and a decrease in virus infection when filopodia formation is inhibited. We describe that HPV16 binding results in the activation of Cdc42 GTPase that in turn results in a...
Source: Viruses - May 26, 2022 Category: Virology Authors: Alyssa Biondo Patricio I. Meneses Tags: Article 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

eIF4E is a critical regulator of human papillomavirus (HPV)-immortalized cervical epithelial (H8) cell growth induced by nicotine.
Abstract Tobacco smoke is known as a cofactor in the development of cervical precancer and cancer caused by human papillomavirus (HPV). The main component in cigarette smoke, nicotine, can be concentrated more strongly in cervical mucus than in blood and it has been implicated as a cocarcinogen that promotes a serial of cancers development through multiple prosurvival pathways. Although the mechanisms of nicotine-induced cell proliferation have been well studied in some epithelial cells, the molecular mechanism of its action in cervical epithelial cells is still unclear. The aims of this study were to investigate ...
Source: Toxicology - March 1, 2019 Category: Toxicology Authors: Chen L, Wang H Tags: Toxicology Source Type: research

Increased expression of PD ‑L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity.
In conclusion, the results presented in the current study suggest that overexpression of PD‑L1, induced by HPV16E7, may be responsible for lymphocyte dysfunction. In addition, soluble PD‑1 may restore the function of tumor‑infiltrating lymphocytes by inhibiting the PD‑L1/PD‑1 signaling pathway. These results may provide a novel insight for immunotherapeutic approaches in the treatment of cervical cancer. PMID: 28075442 [PubMed - as supplied by publisher]
Source: Molecular Medicine Reports - January 12, 2017 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Increased expression of PD-L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity.
In conclusion, the results presented in the current study suggest that overexpression of PD‑L1, induced by HPV16E7, may be responsible for lymphocyte dysfunction. In addition, soluble PD‑1 may restore the function of tumor‑infiltrating lymphocytes by inhibiting the PD‑L1/PD‑1 signaling pathway. These results may provide a novel insight for immunotherapeutic approaches in the treatment of cervical cancer. PMID: 28035385 [PubMed - as supplied by publisher]
Source: Molecular Medicine Reports - January 1, 2017 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells
Abstract Etiological role of viral proteins E6 and E7 of high-risk HPV in cervical carcinogenesis is well established. However, their contribution in chemoresistance and epithelial-mesenchymal transition (EMT) that leads to advanced metastatic lesions and chemoresistance is poorly defined. In the present study, contribution of viral oncoproteins in acquisition of EMT character during onset of chemoresistance was assessed. A chemoresistant cell line (SiHaCR) was developed from an established HPV16-positive cervical cancer cell line, SiHa, by escalating selection pressure of 5-fluorouracil (5-FU). Expression of Survivin, AB...
Source: Tumor Biology - July 23, 2016 Category: Cancer & Oncology 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

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 149: Overexpression of the long non-coding RNA PVT1 and its role in cervical carcinogenesis
Although it is becoming increasingly clear that long non-coding RNAs (lncRNAs) are intricately involved in numerous cancer types, the mechanisms by which they influence carcinogenesis remain poorly understood. The plasmacytoma variant translocation 1 gene (PVT1) is a lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Further, our lab has recently demonstrated that human papillomavirus (HPV) integration, a hallmark of invasive cervical cancer (ICC), into the PVT1 locus occurs in multiple cervical tumors. The present study was designed to investigate the role of PVT1 ...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Iden, M., Fye, S., Ramchandran, R., Rader, J. S. Tags: Molecular and Cellular Biology Source Type: research

Enhanced Radiation Sensitivity in HPV+ Head and Neck Cancer
Patients with human papillomavirus (HPV+)–associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV−) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV− HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV−: 0.59 vs. HPV+: 0.22; P
Source: Cancer Research - July 31, 2013 Category: Cancer & Oncology Authors: Kimple, R. J., Smith, M. A., Blitzer, G. C., Torres, A. D., Martin, J. A., Yang, R. Z., Peet, C. R., Lorenz, L. D., Nickel, K. P., Klingelhutz, A. J., Lambert, P. F., Harari, P. M. Tags: Molecular and Cellular Pathobiology Source Type: research