Roles of dysregulated Notch pathway and small DNA tumor viruses in cancer initiation and progression

Abstract

Notch pathway is a major determinant of cell fate, and research within the last 30 years has shown dysfunctions within this pathway in the majority of solid tumors and leukemias. The molecular mechanisms causing aberrant expression of Notch in cancer are still partially known. Mesotheliomas, breast, and cervical cancers are among the cancer types for which the dysregulation of Notch has been reported together with the association of simian virus 40 (SV40) or human papilloma virus (HPV) infections. In mesotheliomas and cervical cancer, there is clear evidence that these viruses cause and rely on dysregulation of the Notch pathway to promote and sustain cell transformation. The existence of a relationship in tumors between DNA viruses and Notch could have an impact on cancer therapy by implementing Notch inhibition to interfere with the growth of SV40- and HPV-positive cancers. In addition, since Notch links innate and acquired immunity and plays a key role in the regulation of the anti-viral response, targeting Notch in the presence of oncogenic viruses infections may help prevent the onset and progression of cancers associated with the exposure to these viruses.

Keywords

Cancer / human papilloma virus / Notch / pathway / simian virus 40

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