When Viruses Cross Developmental Pathways

Abstract

Aberrant regulation of developmental pathways plays a key role in tumorigenesis. Tumor cells differ from normal cells in their sustained proliferation, replicative immortality, resistance to cell death and growth inhibition, angiogenesis, and metastatic behavior. Often they acquire these features as a consequence of dysregulated Hedgehog, Notch, or WNT signaling pathways. Human tumor viruses affect the cancer cell hallmarks by encoding oncogenic proteins, and/or by modifying the microenvironment, as well as by conveying genomic instability to accelerate cancer development. In addition, viral immune evasion mechanisms may compromise developmental pathways to accelerate tumor growth. Viruses achieve this by influencing both coding and non-coding gene regulatory pathways. Elucidating how oncogenic viruses intersect with and modulate developmental pathways is crucial to understanding viral tumorigenesis. Many currently available antiviral therapies target viral lytic cycle replication but with low efficacy and severe side effects. A greater understanding of the cross-signaling between oncogenic viruses and developmental pathways will improve the efficacy of next-generation inhibitors and pave the way to more targeted antiviral therapies.

Critical roles of cytokine storm and bacterial infection in patients with COVID-19: therapeutic potential of mesenchymal stem cells

“…Notch signaling, a major regulator of the cardiovascular system, has been linked to a range of viral infection-related biological processes. Indeed, Notch pathway regulates a variety of proliferative and differentiation processes in cells, so it's no wonder that viruses that rely on the cell cycle machinery find it appealing (Rizzo et al 2020 ; Breikaa and Lilly 2021 ; Trivedi et al 2021 ). FURIN is a Notch activator that belongs to the protein convertases family.…”

Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers

“…CTNNB1 -mutant HCCs are often low grade and linked with the immune-desert phenotype, while TP53 -mutant HCCs are related to HBV infection [ 72 ]. In addition, the presence of HBV can affect normal liver cell processes when it crosses a developmental pathway, such as Wnt/β-catenin [ 26 , 47 ].…”

“…Infectious agents implicated in PLC development can modulate Wnt pathway molecular components to destabilize normal cell functions [ 47 ]. In fact, oncogenic viruses and bacteria toxins often activate an aberrant Wnt signaling that promotes malignant transformation in target cells [ 24 , 47 ].…”

The Emerging Role of Hedgehog Signaling in Viral Infections

“…As HH signaling is substantially involved in cell proliferation, survival, and immunomodulation, it becomes a preferred target for a variety of viruses to evade antiviral immunity and support viral life cycles (Figure 2). In most virus-related cancers, HH signaling is abnormally activated by viral proteins to drive the tumor initiation process and metastatic cascade (Hanna and Shevde, 2016;Iriana et al, 2021;Trivedi et al, 2021). Inspired by the elegant review of Smelkinson that sheds light on HH signaling as a pathogenic target (Smelkinson, 2017), in the following sections, we will overview the recent progress on the functional interaction between HH signaling and viruses, in the order of virus types.…”