PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications

Aguayo, Francisco; Perez-Dominguez, Francisco; Osorio, Julio; Oliva, Carolina; Calaf, Gloria M.

doi:10.3390/biology12050672

Cited by 12 publications

(6 citation statements)

References 146 publications

(171 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been well documented that E6 and E7 proteins of high-risk human papillomaviruses (HPVs) bind to and degrade p53 and pRb. E6 recruits the intracellular ubiquitin ligase E6AP, which is then ubiquitinated during the assembly of the E6/E6AP/p53 complex and subsequently induces proteasome-dependent p53 degradation ( Li et al., 2019 ), E7 not only inhibits pRb activity but also promotes its degradation ( Mir et al., 2023 ), leading to the loss of their tumor suppressor activities ( Aguayo et al., 2023 ) ( Figure 1 ). The downregulation of these tumor repressors enables uncontrolled cell growth and contributes to HPV-associated cancers, such as cervical cancer.…”

Section: Interaction Between Viral Proteins and Host Proteinsmentioning

confidence: 99%

Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis

Dong,

Wang,

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Virus-induced genomic remodeling and altered gene expression contribute significantly to cancer development. Some oncogenic viruses such as Human papillomavirus (HPV) specifically trigger certain cancers by integrating into the host’s DNA, disrupting gene regulation linked to cell growth and migration. The effect can be through direct integration of viral genomes into the host genome or through indirect modulation of host cell pathways/proteins by viral proteins. Viral proteins also disrupt key cellular processes like apoptosis and DNA repair by interacting with host molecules, affecting signaling pathways. These disruptions lead to mutation accumulation and tumorigenesis. This review focuses on recent studies exploring virus-mediated genomic structure, altered gene expression, and epigenetic modifications in tumorigenesis.

show abstract

Section: Interaction Between Viral Proteins and Host Proteinsmentioning

confidence: 99%

Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis

Dong,

Wang,

et al. 2024

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…In HNSCC, understanding the molecular pathways and predicting patient outcomes is greatly aided by the use of various IHC markers, especially in the context of HPV infection. [11,12]. The role of PIK3CA in HPV-positive oropharyngeal squamous cell carcinoma was studied by Chiosea et al (2013) [13].…”

Section: Immunohistochemical (Ihc) Markers (P53 Pik3ca)mentioning

confidence: 99%

“…Salazar et al (2014) and Smith et al (2010) have identified p53 as important markers associated with survival in HNSCC [ 9 , 10 ]. Aguayo et al (2023) and Kommineni et al (2015) studied the significance of PIK3CA mutations in the PI3K/AKT/mTOR signalling pathway [ 11 , 12 ]. The role of PIK3CA in HPV-positive oropharyngeal squamous cell carcinoma was studied by Chiosea et al (2013) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Relationship of Grade, Stage and Tobacco Usage in Head and Neck Squamous Cell Carcinoma With p53, PIK3CA and MicroRNA Profiles

Kiran,

Chowdhury,

Singh

et al. 2024

Cureus

View full text Add to dashboard Cite

Background: Head and neck squamous cell carcinoma (HNSCC) has multiple epigenetic modifications including post-transcriptional regulation by microRNAs (miRNAs) as well as alterations in molecular pathways due to mutations. Examining these miRNAs and location-specific molecular alterations is essential to understanding the intricacies of HNSCC and directing focused diagnoses and treatments. Aim: To investigate tobacco-related changes in the expression of miRNAs and proteins with clinicopathological parameters of HNSCC and disease-modifying personal habits like tobacco and alcohol use. Methodology: The study concentrated on oropharyngeal cancers using immunohistochemistry and reverse transcription-polymerase chain reaction. Expression of microRNAs mir15a, mir20b, mir21, mir31, mir33b, mir146a, mir155, mir218, mir363 and mir497 and immunohistochemical expression of P53 and PIK3CA were correlated with grade, stage and personal habits like tobacco and alcohol intake. Results: mir21 and mir15a are under-expressed in higher grades with a trend towards statistical significance (P-value of 0.094 and 0.056 by one-way analysis of variance (ANOVA) on ΔC T values). mir155 and mir146a are overexpressed in stage IV tumours while mir 31 is under-expressed in stage IV tumours but statistical significance was not reached. mir497 showed overexpression in tobacco users, but these results were limited by many tumours not showing any amplification for the miRNA and statistical significance was not reached. There was no statistically significant association found between immunohistochemical expression of p53 and PIK3CA with grade, stage or personal habits. Conclusion: Through the deciphering of complex miRNA patterns and their relationships with clinicopathology, this study attempted to increase our understanding of HNSCC. Some candidate miRNAs showing probable association with grade, stage and personal habits were identified, but larger studies are needed to confirm or refute the importance of these miRNAs.

show abstract

“…It has been shown that HPV oncoproteins induce cell cycle progression by inhibiting several tumor suppressors, including p53, PDZ, and retinoblastoma, resulting in tumor initiation and development [ 81 , 82 ]. PI3K/AKT/mTOR pathway, as one of the central signaling routes regulated in HPV‐related cancers, was implicated in regulating cell proliferation, migration, invasion, and angiogenesis [ 83 ]. The over-activation of PI3K/AKT signaling was reported in cervical squamous cell carcinomas like cervical cancer [ 84 ].…”

Section: Introductionmentioning

confidence: 99%

Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis

Letafati,

Taghiabadi,

Zafarian

et al. 2024

Infect Agents Cancer

View full text Add to dashboard Cite

The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies.

show abstract

PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications

Cited by 12 publications

References 146 publications

Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis

Virus-induced host genomic remodeling dysregulates gene expression, triggering tumorigenesis

The Relationship of Grade, Stage and Tobacco Usage in Head and Neck Squamous Cell Carcinoma With p53, PIK3CA and MicroRNA Profiles

Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis

Contact Info

Product

Resources

About