HPV16/18 E5, a promising candidate for cervical cancer vaccines, affects SCPs, cell proliferation and cell cycle, and forms a potential network with E6 and E7

Liao, Shujie; Deng, Dan; Hu, Xiao; Wang, Wei; Li, Li; Li, Wei; Zhou, Jianfeng; Xu, Gang; Li, Meng; Wang, Shixuan; Ma, Ding

doi:10.3892/ijmm.2012.1168

Cited by 13 publications

(10 citation statements)

References 24 publications

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“…In addition, these cells have previously been used in related studies as an acceptable model for the assessment of HPV-infection in cervical cancer [12,14]. However, viral oncogenesis in the presence of the complete HPV genome would present much more complex effects on metabolism, as other HPV oncogenes, such as E7 and E5, would also be expressed and they are known to affect cellular proliferation and differentiation through diverse mechanisms [35]. …”

Section: Discussionmentioning

confidence: 99%

Molecular and Metabolic Consequences Following E6 Transfection in an Isogenic Ovarian Cell Line (A2780) Pair

Chung

Nagy

Zietkowski

et al. 2013

Cell Physiol Biochem

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Aims: To examine molecular and metabolic consequences of HPV-16 viral- protein E6, which targets p53 for degradation, in A2780 (ovarian cancer) cells. Methods: Isogenic derivatives of A2780 cells, with empty-vector (E6-) or E6 (E6+) transfection, were cultured. Intracellular metabolites, fatty acids, and the flux of glutamine, glucose, alanine and lactate in proliferation (Day 2) and confluence (Day 4) were determined using MRS. Western blotting confirmed p53 status, protein expressions related to AKT, ERK and mTOR signalling, and phospholipid metabolism. Results: Growth rate was slower in E6+ cells compared with E6-, resulting in reduced glycolysis, amino acid uptake and fatty acid synthesis. Glutamine metabolism, glycerophosphocholine (GPC), and protein expressions of cytosolic PLA2 (cPLA2) and p-cPLA2 increased in E6+ cells. Despite decreased ERK and AKT signalling, expression of S6RP and p-S6RP downstream of mTOR remained unaffected in E6+ cells. E6+ cells were more invasive and migrate faster than the E6- cells. Conclusion: E6+ had slower growth than E6- cells with reduced metabolism, but E6+ cells maintained cellular homeostasis through glutamine metabolism when compared with E6- at Day 2. The ability to migrate and form larger colonies may provide the E6+ cells with a growth advantage.

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Section: Discussionmentioning

confidence: 99%

Molecular and Metabolic Consequences Following E6 Transfection in an Isogenic Ovarian Cell Line (A2780) Pair

Chung

Nagy

Zietkowski

et al. 2013

Cell Physiol Biochem

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“…Our result is consistent with that described by Liao. In that study, the expression of Mad2 was gradually suppressed from normal to HSIL, and finally CC . While Kim reported that Mad2 overexpression was more frequently in HSIL and CC than that in normal cervix .…”

Section: Discussionmentioning

confidence: 99%

“…Mad2 and BubR1 worked synergistically to exert the biological behavior in most cases. Our result is partially consistent with that described by Liao and Shirnekhi . Liao reported that HPV16/18 E5 could inhibit Mad2 expression, enhance cell proliferation, and facilitate cells enter into S phase.…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of Mad2 and BubR1 increase the malignant potential and nocodazole resistance by compromising spindle assembly checkpoint signaling pathway in cervical carcinogenesis

Wang

Jin

et al. 2019

J of Obstet and Gynaecol

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Aim: To explore the involvement of Mad2 and BubR1 in cervical carcinogenesis. Methods: The expressions of Mad2 and BubR1 in tissues of high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL) and chronic cervicitis were analyzed immunohistochemistrily and compared with those of p16 INK4A . PEGFP-Mad2 and pEGFP-BubR1 were transfected into SiHa cells to overexpress Mad2 and BubR1 and Si-RNAs to knockdown. Cell viability was measured by cell counting kit-8 (CCK-8) assay. Migration and invasion capabilities were detected by Transwell. Propidium iodide staining with flow cytometry was used for cell cycle analysis and apoptosis was detected using Annexin V/7-AAD staining after nocodazole treatment. Results: The expression of Mad2 was significantly lower in HSIL than those in chronic cervicitis and LSIL, however, the expression of BubR1 showed no significant differences. To detect HSIL in cervical lesions, Mad2 had a sensitivity of 88.44% and a specificity of 87.23%, Mad2 was less sensitive and more specific than p16 INK4a . In SiHa cells, knockdown of Mad2 and BubR1 increased cell growth, reinforced invasion capacity and migration potency, inhibited apoptosis and decreased G2-phase distribution after nocodazole treatment. Oppositely, the overexpression strategies made cells show decreased malignant behaviors, raised apoptosis and increased G2-phase distribution. Conclusion: Mad2 negativity was specific to identify HSIL immunohistochemistrily. Downregulation of Mad2 and BubR1 increase the malignant behavior and nocodazole resistance of SiHa cells via causing spindle assembly checkpoint defect. This mechanism may contribute to cervical carcinogenesis and resistance to microtubule-targeting drugs.

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“…HPV16/18 E5 expressing cells have considerably reduced expression of Bub1 and Mad2 [34]. NIH 3T3 cells transfected with the HPV 16 full-length genome and mimetic miR-125b displayed drastic decrease in viral DNA and protein synthesis however, co-transfection with anti-miR-125b and HPV 16 markedly increased HPV DNA [35].…”

Section: Introductionmentioning

confidence: 99%

Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes

2013

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HPV encoded proteins can elicit ectopic protein–protein interactions that re-wire signaling pathways, in a mode that promotes malignancy. Moreover, accumulating data related to HPV is now providing compelling substantiation of a central role played by HPV in escaping immunosurveillance and impairment of apoptotic response. What emerges is an intricate network of Wnt, TGF, Notch signaling cascades that forms higher-order ligand–receptor complexes routing downstream signaling in HPV infected cells. These HPV infected cells are regulated both extracellularly by ligand receptor axis and intracellularly by HPV encoded proteins and impair TRAIL mediated apoptosis. We divide this review into different sections addressing how linear signaling pathways integrate to facilitate carcinogenesis and compounds that directly or indirectly reverse these aberrant interactions offer new possibilities for therapy in cancer. Although HPV encoded proteins mediated misrepresentation of pathways is difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can target dysregulated pathways in HPV infected cervical cancer cells, thus setting the stage for preclinical models and clinical trials.

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HPV16/18 E5, a promising candidate for cervical cancer vaccines, affects SCPs, cell proliferation and cell cycle, and forms a potential network with E6 and E7

Cited by 13 publications

References 24 publications

Molecular and Metabolic Consequences Following E6 Transfection in an Isogenic Ovarian Cell Line (A2780) Pair

Molecular and Metabolic Consequences Following E6 Transfection in an Isogenic Ovarian Cell Line (A2780) Pair

Downregulation of Mad2 and BubR1 increase the malignant potential and nocodazole resistance by compromising spindle assembly checkpoint signaling pathway in cervical carcinogenesis

Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes

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