Abstract IA27: Perturbation of host cellular regulatory networks by human papillomaviruses

Human papillomaviruses (HPVs) are small viruses with ~8,000 bp double-stranded, circular genomes. There are over 200 HPV types and they all infect epithelial cells. While most HPV infections are subclinical others cause overt lesions. Most HPV-associated lesions are benign but some "high-risk" HPVs cause lesions that have a propensity for malignant progression and approximately 10% of all human cancers worldwide are caused by high-risk HPV infections. HPV-associated cancers generally represent non-productive infections, i.e. viral proteins are synthesized but no infectious virus is produced. HPV-associated cancers retain expression of two viral genes, E6 and E7, and continued expression of these two viral genes is necessary for cancer cell proliferation and survival. High-risk HPV E6 and E7 encode small, non-enzymatic proteins of ~150 and ~100 amino acids, respectively. These viral proteins exert their oncogenic activities by associating with and functionally reprogramming critical cellular regulatory nodes; indeed, they have been reported to affect the majority of the "Hallmarks of Cancer" as defined by Hanahan and Weinberg (Cell 144:646). In addition to targeting a number of well-known tumor suppressor pathways including TP53 and RB1, E6 and E7 also, directly and indirectly, affect many other cellular signaling pathways. As a result, HPV E6/E7 expressing cells develop unexpected vulnerabilities to perturbation of signaling pathways that are readily tolerated in normal cells...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Derailed by Infection: Viral-mediated Cell Cycle Dysfunction: Oral Presentations - Invited Abstracts Source Type: research