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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

Th17 Recruitment via Cervical Cancer-Instructed Fibroblasts
In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4+/IL17+ cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell–derived IL6 as an important mediator of paracrine CCL20 inductio...
Source: Cancer Research - December 14, 2015 Category: Cancer & Oncology Authors: Walch–Ruckheim, B., Mavrova, R., Henning, M., Vicinus, B., Kim, Y.–J., Bohle, R. M., Juhasz–Boss, I., Solomayer, E.–F., Smola, S. Tags: Microenvironment and Immunology 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

O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenes.
Authors: Kim M, Kim YS, Kim H, Kang MY, Park J, Lee DH, Roh GS, Kim HJ, Kang SS, Cho GJ, Park JK, Cho JW, Shin JK, Choi WS Abstract O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. We found that depleting OGT with OGT-specific shRNA significantly dec...
Source: Oncotarget - June 23, 2016 Category: Cancer & Oncology Tags: Oncotarget 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

HPV16 E6-E7 induces cancer stem-like cells phenotypes in esophageal squamous cell carcinoma through the activation of PI3K/Akt signaling pathway in vitro and in vivo.
Authors: Xi R, Pan S, Chen X, Hui B, Zhang L, Fu S, Li X, Zhang X, Gong T, Guo J, Zhang X, Che S Abstract High-risk human papillomavirus (HPV), especially HPV16, correlates with cancerogenesis of human esophageal squamous cell carcinoma (ESCC) and we have reported that HPV16 related with a poor prognosis of ESCC patients in China. We aim to investigate the potential role and mechanism of HPV16 in ESCC development and progress. Our following researches demonstrated that ESCC cells which were stably transfected by HPV16 E6-E7 lentiviral vector showed a remarkable cancer stem-like cells (CSCs) phenotype, such as: migr...
Source: Oncotarget - August 6, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

miR-1 inhibits progression of high-risk papillomavirus-associated human cervical cancer by targeting G6PD.
Authors: Hu T, Chang YF, Xiao Z, Mao R, Tong J, Chen B, Liu GC, Hong Y, Chen HL, Kong SY, Huang YM, Xiyang YB, Jin H Abstract Ectopic glucose-6-phosphate dehydrogenase (G6PD) expression may contribute to tumorigenesis in cervical cancer associated with high-risk human papillomavirus (HR-HPV 16 and 18) infections. Here, we demonstrate that microRNA-1 (miR-1) in association with AGO proteins targets G6PD in HR-HPV-infected human cervical cancer cells. miR-1 inhibited expression of a reporter construct containing a putative G6PD 3'-UTR seed region and suppressed endogenous G6PD expression. Down-regulation of miR-1 inc...
Source: Oncotarget - November 20, 2016 Category: Cancer & Oncology Tags: Oncotarget 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

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

Involvement of retinoblastoma-associated protein  48 during photodynamic therapy of cervical cancer cells.
Involvement of retinoblastoma-associated protein 48 during photodynamic therapy of cervical cancer cells. Mol Med Rep. 2017 Jan 26;: Authors: Wu S, Wang L, Ren X, Pan Y, Peng Y, Zou X, Shi C, Zhang Y Abstract 5-Aminolevulinic acid-mediated photodynamic therapy (ALA‑PDT) is an effective treatment option for cervical intraepithelial neoplasia, the precancerous lesion of cervical cancer, and early cervical cancer, particularly for young or nulliparous women who want to remain fertile. A previous report described the involvement of histone deacetylases (HDAC) during ALA‑PDT mediated apoptosis in the c...
Source: Molecular Medicine Reports - February 1, 2017 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Synthetic siRNA targeting human papillomavirus 16 E6: a perspective on in vitro nanotherapeutic approaches
Nanomedicine, Ahead of Print.
Source: Future Medicine: Nanomedicine - January 31, 2018 Category: Nanotechnology Authors: Melissa Togtema Robert Jackson Jessica Grochowski Peter L Villa Miranda Mellerup Jyoti Chattopadhyaya Ingeborg Zehbe Source Type: research