E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Uc, Perla Yaceli; Miranda, Jael; Raya‐Sandino, Arturo; Alarcón, Lourdes; Roldán, María Luisa; Ocadiz-Delgado, Rodolfo; Cortés‐Malagón, Enoc Mariano; Chávez‐Munguía, Bibiana; Ramirez, Georgina; Asomoza, R.; Shoshani, Liora; Gariglio, Patricio; González‐Mariscal, Lorenza

doi:10.3892/ijo.2020.5105

Cited by 4 publications

(4 citation statements)

References 176 publications

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“…The reasons for these phenomena are complex and not fully understood. Similarly, several experimental studies on the role of HPV16 showed that the FVB/N strain is highly sensitive to skin carcinogenesis of mice (Herber et al 1996;Lambert et al 1993), as well as cervical cancer (Uc et al 2020), possibly due to the availability of the E6/E7 proteins in the latter study. To elucidate if the FVB/N genetic background is more suitable for the modulation of the URR11 activity, the mice used in this study were back-crossed from their original B6D2F n genetic background for two generations to FVB/N, resulting of a 75% portion of FVB/N in the genetic pool.…”

Section: Age Of Micementioning

confidence: 80%

“…Effect of the genetic background on transgene expression Woodworth et al (2004) and Uc et al (2020) have shown that the FVB/N genetic background might be suitable for studies on human papillomaviruses, as demonstrated by several mouse models with HPV16, as compared to the C57BL/6 or Balb/c genetic backgrounds. Therefore, the URR11-lacZ mice were backcrossed to the FVB/N genetic background.…”

Section: Urr X E2 Driven Reporter-gene Expressionmentioning

confidence: 99%

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Transgenic HPV11-E2 protein modulates URR activity in vivo

et al. 2023

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In vitro experiments have shown that the E2 protein of human papillomaviruses (HPV) binds to the upstream regulatory region (URR) of the viral genome and modulates transcription. Additionally, it seems to be a necessary component for viral DNA replication together with E1. We have developed a transgenic mouse model containing the URR region of the low-risk virus HPV11 that regulates the expression of the lacZ reporter gene. Most interestingly, in these mice, the transgene was exclusively expressed in the bulge region of the hair follicle but not in any other tissues. Further experimental data indicate that in double transgenic mice that also express the HPV11-E2 protein under the control of the Ubiquitin C-promoter, the transcription of the reporter gene is modulated. When E2 is present, the expression of the reporter gene also occurs exclusively in the bulge region of the hair follicles as it does in the single transgenic mice, but the expression of the lacZ driven by the URR is increased and the statistical spread is greater. Even if the expression of the reporter gene occurs in the hair follicles of the dorsal skin of an animal uniform, E2 obviously has the capacity for both to induce and to repress the URR activity in vivo.

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Section: Age Of Micementioning

confidence: 80%

Section: Urr X E2 Driven Reporter-gene Expressionmentioning

confidence: 99%

Transgenic HPV11-E2 protein modulates URR activity in vivo

et al. 2023

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“…Hence, we analyzed if the absence of ZO-2 altered claudin-4 expression in cells cultured on NRA. We analyzed claudin-4, since previous reports had shown that it is more abundant in MDCK cells, stably expressing E7 oncoprotein from human papillomavirus 16 [ 45 ], and displays an altered pattern of expression in a wide variety of carcinomas (for review, see [ 46 ]). Figure 12 A shows that 24 h after parental and ZO-2 KD cells were plated on NRA, in comparison to the flat surface of coverslips, claudin-4 expression in the cytoplasmic vesicles augmented, both in sparse and confluent cultures.…”

Section: Resultsmentioning

confidence: 99%

The Role of ZO-2 in Modulating JAM-A and γ-Actin Junctional Recruitment, Apical Membrane and Tight Junction Tension, and Cell Response to Substrate Stiffness and Topography

Pinto-Dueñas,

Hernández-Guzmán,

Marsch

et al. 2024

IJMS

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This work analyzes the role of the tight junction (TJ) protein ZO-2 on mechanosensation. We found that the lack of ZO-2 reduced apical membrane rigidity measured with atomic force microscopy, inhibited the association of γ-actin and JAM-A to the cell border, and instead facilitated p114RhoGEF and afadin accumulation at the junction, leading to an enhanced mechanical tension at the TJ measured by FRET, with a ZO-1 tension probe, and increased tricellular TJ tension. Simultaneously, adherens junction tension measured with an E-cadherin probe was unaltered. The stability of JAM-A and ZO-2 binding was assessed by a collaborative in silico study. The absence of ZO-2 also impacted the cell response to the substrate, as monolayers plated in 20 kPa hydrogels developed holes not seen in parental cultures and displayed a retarded elongation and formation of cell aggregates. The absence of ZO-2 was sufficient to induce YAP and Snail nuclear accumulation in cells cultured over glass, but when ZO-2 KD cells were plated in nanostructured ridge arrays, they displayed an increased abundance of nuclear Snail and conspicuous internalization of claudin-4. These results indicate that the absence of ZO-2 also impairs the response of cells to substrate stiffness and exacerbates transformation triggered by substrate topography.

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“…Researches have clari ed that tight junction might play an import part in HPV-related diseases. E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions, accompanying by a reduced expression of claudins -1, -2 and -10, and an increase in claudin-4 [42]. Additionally, in HPV positive tumor cells, E6-mediated inhibition of MAGI-1 function contributes to HPVinduced malignancy by perturbing tight junction assembly with concomitant stimulation of proliferation and inhibition of apoptosis [43,44].…”

Section: Igf2bp3 Was Related To the Tight Junctions In Hpv-related Cescmentioning

confidence: 99%

IGF2BP3 is associated with HPV status and tight junction in HPV-related cervical cancer

Han

Han#

et al. 2023

Preprint

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Background Although m6A modification was known to have broad effects on malignant tumors by participating in tumor proliferation, differentiation, tumorigenesis, invasion and metastasis, as oncogenes or anti-oncogenes, their effects of microbes in cancers have been rarely disputed. To investigate the function of IGF2BP3, one of the indispensable regulators of m6A, in HPV virus invading and transmitting, integrative analyses was performed in this study and identified that it was highly expressed in tumors and was related to the poor prognosis in CESC. Methods We investigate the expresseion level of IGF2BP3 and its prognostic value in CESC via multiple datasets including TCGA, GTEx datasets and TIMER. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed genes were performed using GOplot, org.Hs.eg.db and clusterProfiler packages and visualized using the ggplot2 package Results In HPV-positive tumors, IGF2BP3 was positively associated with tumor HPV status. Further analysis demonstrated that IGF2BP3 high status was correlated with signaling pathways related to cell-cell and cell-ECM interactions, including receptor ligand activity, neuroactive ligand receptor interaction and chemical carcinogenesis receptor activation. Moreover, correlation analysis showed that IGF2BP3 would impair the formation of cell polarity and cell-cell contacts by dysregulating the expression of tight junction molecules. Conclusions Our results identified that IGF2BP3 high status, is associated with poor prognosis and HPV status, and IGF2BP3 serves as a mediator of the tight junction formation in HPV-associated cancer, which provides a promising therapeutic target for anti-cancer schedule.

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E7 oncoprotein from human papillomavirus 16 alters claudins expression and the sealing of epithelial tight junctions

Cited by 4 publications

References 176 publications

Transgenic HPV11-E2 protein modulates URR activity in vivo

Transgenic HPV11-E2 protein modulates URR activity in vivo

The Role of ZO-2 in Modulating JAM-A and γ-Actin Junctional Recruitment, Apical Membrane and Tight Junction Tension, and Cell Response to Substrate Stiffness and Topography

IGF2BP3 is associated with HPV status and tight junction in HPV-related cervical cancer

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