Proteases and HPV-Induced Carcinogenesis

Vieira, Gabriel Viliod; Santos, Fernanda Somera dos; Lepique, Ana Paula; Fonseca, Carol Kobori da; Innocentini, Lara Maria Alencar Ramos; Braz‐Silva, Paulo Henrique; Quintana, Silvana Maria; Sales, Katiuchia Uzzun

doi:10.3390/cancers14133038

Cited by 15 publications

(9 citation statements)

References 267 publications

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“…4A ). p53 is the direct target of HPV E6, and most of the carcinogenic functions of HPV E6 are realised via its influence on p53 [ 48 , 49 , 50 , 51 ]. To investigate whether HPV E6 affects MDH1 via its impact on p53 expression, we overexpressed and then knocked down p53 in ESCC cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

HPV18 E6 inhibits α‐ketoglutarate‐induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway

et al. 2023

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Oncogene E6 plays a critical role in the development and progression of esophageal cancer caused by human papillomavirus (HPV) infection. Alpha‐ketoglutarate (AKG) is a key metabolite in the tricarboxylic acid cycle and has been widely used as a dietary and anti‐ageing supplement. In this study, we found that treating esophageal squamous carcinoma cells with a high dose of AKG can induce cell pyroptosis. Furthermore, our research confirms that HPV18 E6 inhibits AKG‐induced pyroptosis of esophageal squamous carcinoma cells by lowering P53 expression. P53 downregulates malate dehydrogenase 1 (MDH1) expression; however, MDH1 downregulates L‐2‐hydroxyglutarate (L‐2HG) expression, which inhibits a rise in reactive oxygen species (ROS) levels—as L‐2HG is responsible for excessive ROS. This study reveals the actuating mechanism behind cell pyroptosis of esophageal squamous carcinoma cells induced by high concentrations of AKG, and we posit the molecular pathway via which the HPV E6 oncoprotein inhibits cell pyroptosis.

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Section: Resultsmentioning

confidence: 99%

HPV18 E6 inhibits α‐ketoglutarate‐induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway

et al. 2023

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“…In this study, we established and characterized immortalized HDPCs via E6/E7 transfection. E6 and E7 oncoproteins from high-risk HPV16 inhibit p53 and pRb, respectively, and thereby enable cellular immortalization [ 16 ]. Full-length E6 open reading frames (ORF) (450 bp) and truncated E6 ORFs including E6*I (300 bp) and E6*II (150 bp) are generated by splicing of HPV16 E6 [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of Immortalized Human Dermal Papilla Cells Expressing Human Papillomavirus 16 E6/E7

Kim,

Jeon,

Park

et al. 2023

J. Microbiol. Biotechnol.

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Primary human dermal papilla cells (HDPCs) are often preferred in studies on hair growth and regeneration. However, primary HDPCs are limited by their reduced proliferative capacity, decreased hair induction potential, and extended doubling times at higher passages. To overcome these limitations, pTARGET vectors containing human papillomavirus16 (HPV16) E6/E7 oncogenes were transfected into HDPCs and selected using G-148 to generate immortalized cells here. HPV16 E6/E7 oncogenes were efficiently transfected into primary HDPCs. Immortalized HDPC showed higher proliferative activity than primary HDPC, confirming an increased proliferation rate. Expression of p53 and pRb proteins was downregulated by E6 and E7, respectively. E6/E7 expressing HDPC cells revealed that cyclin-dependent kinase (CDK) inhibitor p21 expression was decreased, while cell cycle-related genes and proteins (CDK2 and cyclin E) and E2F family genes were upregulated. Immortalized HDPCs maintained their responsiveness to Wnt/β-catenin pathway and hair follicle formation capability, as indicated by their aggregative properties and stemness. E6/E7 immortalized HDPCs may facilitate in vitro hair growth and regeneration studies.

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“…Hr-HPVs express E6 and E7, two major oncoproteins, which are responsible for the inhibition of p53 and pRB proteins in human keratinocytes and cellular immortalization (Figure 2). p53 and pRB proteins are responsible for the regulation of many key signaling pathways and gene expression [28]. HPV-associated malignancies differ from their non-HPV counterparts.…”

Section: Hpv and Associated Malignanciesmentioning

confidence: 99%

Human Papilloma Virus: An Unraveled Enigma of Universal Burden of Malignancies

Khan

Harshithkumar

et al. 2023

Pathogens

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HPV, or Human Papilloma Virus, has been the primary causative agent of genital warts and cervical cancer worldwide. It is a sexually transmitted infection mainly affecting women of reproductive age group, also infecting men and high-risk group individuals globally, resulting in high mortality. In recent years, HPV has also been found to be the major culprit behind anogenital cancers in both gender and oropharyngeal and colorectal cancers. Few studies have reported the incidence of HPV in breast cancers as well. For a few decades, the burden of HPV-associated malignancies has been increasing at an alarming rate due to a lack of adequate awareness, famine vaccine coverage and hesitancy. The effectiveness of currently available vaccines has been limited to prophylactic efficacy and does not prevent malignancies associated with post-exposure persistent infection. This review focuses on the current burden of HPV-associated malignancies, their causes and strategies to combat the growing prevalence of the cancers. With the advent of new technologies associated with treatment pertaining to therapeutic interventions and employing effective vaccine coverage, the burden of this disease may be reduced in the population.

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Proteases and HPV-Induced Carcinogenesis

Cited by 15 publications

References 267 publications

HPV18 E6 inhibits α‐ketoglutarate‐induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway

HPV18 E6 inhibits α‐ketoglutarate‐induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway

Establishment and Characterization of Immortalized Human Dermal Papilla Cells Expressing Human Papillomavirus 16 E6/E7

Human Papilloma Virus: An Unraveled Enigma of Universal Burden of Malignancies

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