Matrix metalloproteinases (MMPs) are a member of the protein family intimately associated with zinc-containing endopeptidases, which are the main proteases implicated in extracellular matrix (ECM) degradation. The high ability of MMPs in the degradation of extracellular proteins is an important event in many normal biological as well as pathologic processes, including tumor progression, tissue repair, wound healing, developmental morphogenesis, and inflammatory diseases. This review is focused on the description of the modulation mechanism of MMPs via oncoviruses. Up to now, a large number of oncogenic viruses have been detected and recognized as etiologic factors of multiple human cancers. Actually, by expression of several viral oncoproteins of tumorigenic viruses with the simple genetic system, we are able to deregulate or modulate the pathways of cell transformation procedure in malignancy. In brief, upregulated expression of MMPs genes by direct (through DNA binding) , as well as indirect interactions (by activating PI-3K/AKT, ERK/MAPK, IFN/JAK/STAT, JNK, NF-κB signaling pathways and/or immune response) with tumorigenic viruses, have a noticeable role in the proliferation of cells, as well as angiogenesis, mobility, EMT, invasiveness, and metastatic features. In fact, the growth of tumor-related researchers offers a future perspective for the efficiency of targeted, molecular-based therapies and its anticancer effects via diverse mechanisms such as the suppression of viral oncoproteins.
Hippo signaling has been recognized as a newly identified tumor suppressor signaling pathway that can regulate cellular processes including regeneration, cell death, differentiation, and development. Its dysregulation through overexpression of YAP (Yes-associated protein) and TAZ (PDZ-binding motif) as two main oncogenic factors of the Hippo pathway has a crucial role in several cancers. Because of the limited prognosis and therapeutic targets, further understanding of molecular pathways involved in tumorigenesis is one of the interesting issues in studies. Here, we demonstrated that some viruses, through dysregulation of the Hippo signaling pathway can be implicated in transformation, metastasis, and chemotherapeutic drug resistance in virus-related cancer and also help processes involved in the pathogenesis of viral infection such as persistence.
