FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4211219113> ?p ?o ?g. }

• W4211219113 abstract "Head and Neck cancer (HNC) is a fatal malignancy with poor prognosis. Human Papillomavirus (HPV) infection is becoming the prominent cause of HNC in the western world, and studying the molecular mechanisms underlying its action in cancers is key towards targeted therapy. To replicate, HPV regulates the host DNA damage repair (DDR) pathway. SMAD4 is also involved in the regulation of the DDR machinery and likely plays important role in maintaining cell viability upon genotoxic stress. In this study, we investigated the role of HPV in the upregulation of SMAD4 to control the DDR response and facilitate its lifecycle.SMAD4, Rad51 and CHK1 expression was assessed in HPV-positive and HPV-negative HNC using TCGA data, a panel of 14 HNC cell lines and 8 fresh tumour tissue samples from HNC patients. HPV16 expression was modulated by E6/E7 siRNA knock-down or transduction in HPV-positive HNC cell lines and Human Primary keratinocytes respectively. SMAD4 half-life was assessed by cycloheximide treatment in HNC cell lines, together with βTRCP1-dependent SMAD4 ubiquitination. SMAD4 siRNA knock-down was used to determine its role in HPV-mediated regulation of DDR machinery and to assess cisplatin sensitivity in HPV-positive HNC cell lines.We found that HPV increases SMAD4 expression is both HPV-positive HNC tumours and cell lines, impairing its degradation which is mediated by the E3 ubiquitin ligase βTRCP1. SMAD4 expression highly correlates with the expression of two main players of the DDR pathway, CHK1 and Rad51, which expression is also upregulated by the presence of HPV. In particular, we demonstrate that HPV stabilizes SMAD4 to increase CHK1 and Rad51 expression. In addition, SMAD4-deficient HPV-positive cells have increased sensitivity to cisplatin treatment.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." @default.
• W4211219113 created "2022-02-13" @default.
• W4211219113 creator A5026027878 @default.
• W4211219113 creator A5026382309 @default.
• W4211219113 creator A5042423774 @default.
• W4211219113 creator A5051482541 @default.
• W4211219113 creator A5057050144 @default.
• W4211219113 creator A5086400503 @default.
• W4211219113 creator A5089501565 @default.
• W4211219113 date "2022-02-10" @default.
• W4211219113 modified "2023-10-13" @default.
• W4211219113 title "HPV-mediated regulation of SMAD4 modulates the DNA damage response in head and neck cancer" @default.
• W4211219113 cites W1502943587 @default.
• W4211219113 cites W1899713877 @default.
• W4211219113 cites W1927461076 @default.
• W4211219113 cites W1964636114 @default.
• W4211219113 cites W1965635324 @default.
• W4211219113 cites W1969210627 @default.
• W4211219113 cites W1976121428 @default.
• W4211219113 cites W1981244332 @default.
• W4211219113 cites W1983334162 @default.
• W4211219113 cites W1998612778 @default.
• W4211219113 cites W2000313986 @default.
• W4211219113 cites W2002803108 @default.
• W4211219113 cites W2004627796 @default.
• W4211219113 cites W2007783646 @default.
• W4211219113 cites W2037038224 @default.
• W4211219113 cites W2045640538 @default.
• W4211219113 cites W2050847569 @default.
• W4211219113 cites W2056374271 @default.
• W4211219113 cites W2075300416 @default.
• W4211219113 cites W2081116295 @default.
• W4211219113 cites W2090272354 @default.
• W4211219113 cites W2092800030 @default.
• W4211219113 cites W2100801124 @default.
• W4211219113 cites W2109614413 @default.
• W4211219113 cites W2112267492 @default.
• W4211219113 cites W2114008428 @default.
• W4211219113 cites W2114843025 @default.
• W4211219113 cites W2122441872 @default.
• W4211219113 cites W2138078109 @default.
• W4211219113 cites W2139721691 @default.
• W4211219113 cites W2141828493 @default.
• W4211219113 cites W2149441684 @default.
• W4211219113 cites W2297685225 @default.
• W4211219113 cites W2411905793 @default.
• W4211219113 cites W2592591707 @default.
• W4211219113 cites W2742084573 @default.
• W4211219113 cites W2744412017 @default.
• W4211219113 cites W2759119425 @default.
• W4211219113 cites W2793226176 @default.
• W4211219113 cites W2912894367 @default.
• W4211219113 cites W2942435715 @default.
• W4211219113 cites W2980221048 @default.
• W4211219113 cites W3010406759 @default.
• W4211219113 cites W3015706388 @default.
• W4211219113 doi "https://doi.org/10.1186/s13046-022-02258-9" @default.
• W4211219113 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35144669" @default.
• W4211219113 hasPublicationYear "2022" @default.
• W4211219113 type Work @default.
• W4211219113 citedByCount "10" @default.
• W4211219113 countsByYear W42112191132022 @default.
• W4211219113 countsByYear W42112191132023 @default.
• W4211219113 crossrefType "journal-article" @default.
• W4211219113 hasAuthorship W4211219113A5026027878 @default.
• W4211219113 hasAuthorship W4211219113A5026382309 @default.
• W4211219113 hasAuthorship W4211219113A5042423774 @default.
• W4211219113 hasAuthorship W4211219113A5051482541 @default.
• W4211219113 hasAuthorship W4211219113A5057050144 @default.
• W4211219113 hasAuthorship W4211219113A5086400503 @default.
• W4211219113 hasAuthorship W4211219113A5089501565 @default.
• W4211219113 hasBestOaLocation W42112191131 @default.
• W4211219113 hasConcept C104317684 @default.
• W4211219113 hasConcept C121608353 @default.
• W4211219113 hasConcept C127561419 @default.
• W4211219113 hasConcept C134459356 @default.
• W4211219113 hasConcept C134935766 @default.
• W4211219113 hasConcept C143425029 @default.
• W4211219113 hasConcept C190283241 @default.
• W4211219113 hasConcept C25602115 @default.
• W4211219113 hasConcept C2779012473 @default.
• W4211219113 hasConcept C502942594 @default.
• W4211219113 hasConcept C54355233 @default.
• W4211219113 hasConcept C552990157 @default.
• W4211219113 hasConcept C555283112 @default.
• W4211219113 hasConcept C81885089 @default.
• W4211219113 hasConcept C86803240 @default.
• W4211219113 hasConcept C97037327 @default.
• W4211219113 hasConceptScore W4211219113C104317684 @default.
• W4211219113 hasConceptScore W4211219113C121608353 @default.
• W4211219113 hasConceptScore W4211219113C127561419 @default.
• W4211219113 hasConceptScore W4211219113C134459356 @default.
• W4211219113 hasConceptScore W4211219113C134935766 @default.
• W4211219113 hasConceptScore W4211219113C143425029 @default.
• W4211219113 hasConceptScore W4211219113C190283241 @default.
• W4211219113 hasConceptScore W4211219113C25602115 @default.
• W4211219113 hasConceptScore W4211219113C2779012473 @default.
• W4211219113 hasConceptScore W4211219113C502942594 @default.
• W4211219113 hasConceptScore W4211219113C54355233 @default.
• W4211219113 hasConceptScore W4211219113C552990157 @default.

• next