Deregulation of the Notch pathway as a common road in viral carcinogenesis.

ABSTRACT

The Notch pathway is a conserved signaling pathway and a form of direct cell-cell communication related to many biological processes during development and adulthood. Deregulation of the Notch pathway is involved in many diseases, including cancer. Almost 20% of all cancer cases have an infectious etiology, with viruses responsible for at least 1.5 million new cancer cases per year. Seven groups of viruses have been classified as oncogenic hepatitis B and C viruses (HBV and HCV respectively), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), human T lymphotropic virus (HTLV-1), human papillomavirus (HPV), and Merkel cell polyomavirus (MCPyV). These viruses share the ability to manipulate a variety of cell pathways that are critical in proliferation and differentiation, leading to malignant transformation. Viral proteins interact directly or indirectly with different members of the Notch pathway, altering their normal function. This review focuses exclusively on the direct interactions of viral oncoproteins with Notch elements, providing a deeper understanding of the dual behavior of the Notch pathway as activator or suppressor of neoplasia in virus-related cancers.