Impact of HPV E5 on viral life cycle via EGFR signaling

Ilahi, Naureen Ehsan; Bhatti, Attya

doi:10.1016/j.micpath.2019.103923

Cited by 39 publications

(44 citation statements)

References 105 publications

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“…EGFR is a transmembrane protein that is activated by the binding of some ligands, in particular the epithelial growth factor (EGF), the transforming High EGFR expression is associated with poor prognosis in cervical cancer [41]. The HPV oncoprotein E5 is involved in the activation and increase of the EGFR pathway dependently on the ligand (Figure 1c) [42]. Viral oncoprotein E5 can upregulate VEGF (vascular endothelial growth factor) and cyclooxygenase 2 through EGFR [43].…”

Section: Egfrmentioning

confidence: 99%

Human Papillomavirus and Cellular Pathways: Hits and Targets

2021

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The Human Papillomavirus (HPV) is the causative agent of different kinds of tumors, including cervical cancers, non-melanoma skin cancers, anogenital cancers, and head and neck cancers. Despite the vaccination campaigns implemented over the last decades, we are far from eradicating HPV-driven malignancies. Moreover, the lack of targeted therapies to tackle HPV-related tumors exacerbates this problem. Biomarkers for early detection of the pathology and more tailored therapeutic approaches are needed, and a complete understanding of HPV-driven tumorigenesis is essential to reach this goal. In this review, we overview the molecular pathways implicated in HPV infection and carcinogenesis, emphasizing the potential targets for new therapeutic strategies as well as new biomarkers.

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Section: Egfrmentioning

confidence: 99%

Human Papillomavirus and Cellular Pathways: Hits and Targets

2021

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“…Also, E5 binds the 16 kDa subunit C of the V-H+-ATPase inhibits the degradation of EGFR. c-Cbl as a ubiquitin ligase associates with the activated EGFR and targets it for degradation was hijacked by E5 [38][39][40]. To sum up, E5 is essential to trigger the EGFR pathway.…”

Section: Egfr Blockade Is Not a Good Choice For Hpv-positive Hnsccmentioning

confidence: 99%

Therapeutic strategies of different HPV status in Head and Neck Squamous Cell Carcinoma

Sun¹,

Wang²,

Qiu³

et al. 2021

Int. J. Biol. Sci.

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Head and neck squamous cell carcinoma (HNSCC) is the 9 th most common malignant tumor in the world. Based on the etiology, HNSCC has two main subtypes: human papillomavirus (HPV)-related and HPV-unrelated. HPV-positive HNSCC is more sensitive to treatment with favorable survival. Due to the different biological behaviors, individual therapy is necessary and urgently required to deduce the therapeutic intensity of HPV-positive disease and look for a more effective and toxicity-acceptable regimen for HPV-negative disease. EGFR amplification and PI3K/AKT/mTOR pathway aberrant activation are quite common in HPV-positive HNSCC. Besides, HPV infection alters immune cell infiltrating in HNSCC and encompasses a diverse and heterogeneous landscape with more immune infiltration. On the other hand, the chance of HPV-negative cancers harboring mutation on the P53 gene is significantly higher than that of HPV-positive disease. This review focuses on the updated preclinical and clinical data of HPV-positive and HPV-negative HNSCC and discusses the therapeutic strategies of different HPV status in HNSCC.

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“…In oncogenic HPV, E4 disrupts the cytokeratin network, thus facilitating viral escape from infected epithelial surfaces (Doorbar, 2013). E5 enhances growth factor signaling pathways like EGFR activation which promotes cell proliferation and inhibits keratinocyte differentiation (DiMaio & Mattoon, 2001;Ilahi et al 2020;McBride, 2017). The E6 and E7 proteins drive HPV-infected cells to re-enter the cell cycle and synthesize DNA.…”

Section: The Hpv Genomementioning

confidence: 99%

Human papillomavirus-mediated carcinogenesis and tumor progression

Abboodi

Delva

Emmel

et al. 2021

GENOME INSTAB. DIS.

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High-risk human papillomaviruses (HPV) cause 5% of all human cancers and are primary etiologic agents of cervical, anal, and oropharyngeal cancer. HPV infection is necessary, but not sufficient per se to produce cancer: additional changes must occur that transform HPV-infected cells to malignancy. The HPV oncoproteins E6 and E7 immortalize human keratinocytes, cervical cells, and fibroblasts in culture. Each oncoprotein interacts with a variety of cellular binding partners; most important for transformation are E6 and E7's interactions with p53 and RB (respectively) which lead to degradation of p53 and RB through the ubiquitin pathway. Inactivation of p53 and RB leads to inactivation of pivotal cell cycle checkpoints, thereby stimulating cell proliferation and allowing cell division to occur independently of the presence of DNA damage, replicative stress, and other such insults, leading to genome instability. Continuous expression of E6/E7 drives the proliferation and progression of most HPV-mediated cancers of the cervix and a substantial fraction of those of the oropharynx. However, at both cancer sites, "HPV-inactive" tumors that contain HPV DNA, but do not express E6/E7 arise. We propose that these HPV-inactive cancers begin as HPV-driven lesions, but lose E6/E7 expression at some point during progression. We have recently shown that p53 deletion in HPV-immortalized, premalignant cells allows for the emergence of cell populations that no longer express E6/E7. These findings corroborate the notion of a pivotal role of p53 in the context of HPV-mediated transformation, both at the initiation and progression stages of cancer development.

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Impact of HPV E5 on viral life cycle via EGFR signaling

Cited by 39 publications

References 105 publications

Human Papillomavirus and Cellular Pathways: Hits and Targets

Human Papillomavirus and Cellular Pathways: Hits and Targets

Therapeutic strategies of different HPV status in Head and Neck Squamous Cell Carcinoma

Human papillomavirus-mediated carcinogenesis and tumor progression

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