Metabolic Reprogramming in Cancer: Role of HPV 16 Variants

Arizmendi-Izazaga, Adán; Navarro-Tito, Napoleón; Jiménez‐Wences, Hilda; Mendoza-Catalán, Miguel Ángel; Martínez‐Carrillo, Dinorah Nashely; Leyva‐Vázquez, Marco Antonio; Olea-Flores, Monserrat; Dircio-Maldonado, Roberto; Torres-Rojas, Francisco I; Soto-Flores, Diana G.; Illades‐Aguiar, Berenice; Ortíz-Ortíz, Julio

doi:10.3390/pathogens10030347

Cited by 19 publications

(17 citation statements)

References 174 publications

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“…Interestingly, HPV-16 variants can interact with multiple metabolic proteins favoring the Warburg effect. 25…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, HPV-16 variants can interact with multiple metabolic proteins favoring the Warburg effect. 25 We also analyzed the distribution of positivity in the thickness of the epithelium. In this sense, GLUT1 expression is present in the cellular membrane in two thirds of the epithelium and in all epithelium thickness in samples from women with CIN.…”

Section: Discussionmentioning

confidence: 99%

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GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

Reyna-Hernández¹,

Alarcón‐Romero²,

Ortíz-Ortíz³

et al. 2022

J Histochem Cytochem.

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Metabolic reprogramming is typical in cancerous cells and is required for proliferation and cellular survival. In addition, oncoproteins of high-risk human papillomavirus (HR-HPV) are involved in this process. This study evaluated the relationship between glucose transporter I (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter type 4 (MCT4) expression and cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) with HR-HPV infection. The protein expression was evaluated in women with CIN I ( n=20), CIN II/III ( n=16), or ICC ( n=24) by immunohistochemistry. The protein expression was analyzed qualitatively by van Zummeren score and quantitatively by Image ProPlus 6 software. LDHA expression increases in HPV-16 infection. In the CIN I group, GLUT1 immunostaining has a 35% protein expression at the membrane level at more than two thirds of the epithelium, which increased by 21.25% more in CIN II/III in more than two thirds of the epithelium. While LDHA and MCT4 in CIN I mostly do not present immunostaining, or this was only limited to the basal stratum, this expression is increased in CIN II/III and ICC cases. The GLUT1, LDHA, and MCT4 expression increased in ICC. The overexpression in high-grade CIN with HR-HPV infection shows a higher risk for cervical carcinoma progression.

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“…Interestingly, HPV-16 variants can interact with multiple metabolic proteins favoring the Warburg effect. 25…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

Reyna-Hernández¹,

Alarcón‐Romero²,

Ortíz-Ortíz³

et al. 2022

J Histochem Cytochem.

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“…Metabolic reprogramming is an important hallmark in cancer [ 13 ]. However, the mechanisms of how HPV viral oncoproteins alter cell metabolism to satisfy their own energy demands and how this may contribute to tumorigenesis remain unknown [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, recent studies have suggested that the HPV oncogenes E5, E6, and E7 play critical roles in the development of chronic inflammation through various mechanisms and can affect the redox homeostasis of host cells, inducing oxidative stress, which may promote viral integration and cancer development [ 11 , 12 ]. Moreover, the oncoproteins HPV16 E6 and E7 regulate the cell metabolism to satisfy the energy demands necessary for persistent infection and development of cervical cancer [ 13 ]. However, the gene expression profiles of the oncogene HPV8 E7 in human epidermal keratinocytes remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7

Chen

Tang

et al. 2022

Pathol. Oncol. Res.

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Background: Human papillomavirus type 8 (HPV8) has been implicated in the progress of non-melanoma skin cancers and their precursor lesions. The HPV8 E7 oncoprotein plays a key role in the tumorigenesis of HPV-associated cutaneous tumors. However, the exact role of HPV8 E7 in human epidermal carcinogenesis has not been fully elucidated.Methods: To investigate the potential carcinogenic effects of HPV8 E7 on epithelial cells, we used RNA-sequencing technology to analyze the gene expression profile of HPV8 E7-overexpressed normal human epidermal keratinocytes (NHEKs).Results: RNA-sequencing revealed 831 differentially expressed genes (DEGs) between HPV8 E7-expressing NHEKs and control cells, among which, 631 genes were significantly upregulated, and 200 were downregulated. Gene ontology annotation enrichment analysis showed that HPV8 E7 mainly affected the expression of genes associated with protein heterodimerization activity, DNA binding, nucleosomes, and nucleosome assembly. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that overexpression of HPV8 E7 affected the expression of gene clusters associated with viral carcinogenesis and transcriptional misregulation in cancer and necroptosis signaling pathways that reportedly play crucial roles in HPV infection promotion and cancer progression. We also found the DEGs, such as HKDC1 and TNFAIP3, were associated with epigenetic modifications, immune regulation, and metabolic pathways.Conclusion: Our results demonstrate that the pro-carcinogenic effect of HPV8 expression in epithelial cells may be attributed to the regulatory effect of oncogene E7 on gene expression associated with epigenetic modifications and immune and metabolic status-associated gene expression. Although our data are based on an in vitro experiment, it provides the theoretical evidence that the development of squamous cell carcinoma can be caused by HPV.

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“…However, another study of patient tissues found that HPV integration within the tonsillar crypt was associated with MYC amplification and overexpression [ 78 ]. The upregulation of MYC by HPV, predominantly enacted through the E6 oncoprotein [ 68 ], could serve to increase the expression of metabolic genes involved in glycolysis, glutaminolysis and nucleotide synthesis [ 79 ], but this remains to be conclusively determined.…”

Section: Regulation Of Myc By Dna Tumor Virus Oncoproteinsmentioning

confidence: 99%

Metabolic Control by DNA Tumor Virus-Encoded Proteins

Prusinkiewicz

Mymryk

2021

Pathogens

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Viruses co-opt a multitude of host cell metabolic processes in order to meet the energy and substrate requirements for successful viral replication. However, due to their limited coding capacity, viruses must enact most, if not all, of these metabolic changes by influencing the function of available host cell regulatory proteins. Typically, certain viral proteins, some of which can function as viral oncoproteins, interact with these cellular regulatory proteins directly in order to effect changes in downstream metabolic pathways. This review highlights recent research into how four different DNA tumor viruses, namely human adenovirus, human papillomavirus, Epstein–Barr virus and Kaposi’s associated-sarcoma herpesvirus, can influence host cell metabolism through their interactions with either MYC, p53 or the pRb/E2F complex. Interestingly, some of these host cell regulators can be activated or inhibited by the same virus, depending on which viral oncoprotein is interacting with the regulatory protein. This review highlights how MYC, p53 and pRb/E2F regulate host cell metabolism, followed by an outline of how each of these DNA tumor viruses control their activities. Understanding how DNA tumor viruses regulate metabolism through viral oncoproteins could assist in the discovery or repurposing of metabolic inhibitors for antiviral therapy or treatment of virus-dependent cancers.

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Metabolic Reprogramming in Cancer: Role of HPV 16 Variants

Cited by 19 publications

References 174 publications

GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

GLUT1, LDHA, and MCT4 Expression Is Deregulated in Cervical Cancer and Precursor Lesions

Gene Expression Profile Analysis of Human Epidermal Keratinocytes Expressing Human Papillomavirus Type 8 E7

Metabolic Control by DNA Tumor Virus-Encoded Proteins

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