生化学および細胞生物学ジャーナル

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A New Era in Toxicology Research: Systems Biology and Synthetic Biology Calreticulin's Biological Functions in Cancer

Yang Jinxi

Systems biology and synthetic biology are emerging disciplines that are increasingly being used in various areas of bioscience. Toxicology is starting to benefit from systems biology, and we believe it will benefit from synthetic biology in the future. As a result, a new epoch is on the horizon. This review demonstrates how a suite of novel techniques and tools can be used to better understand complex health and toxicology issues. We discuss the limitations of traditional computational approaches to toxicology and epidemiology research, using polycyclic aromatic hydrocarbons (PAHs) and their effects on adverse birth outcomes as an example. We discuss how systems toxicology (and its subdisciplines,genomic, proteomic, and metabolomic toxicology) can help to overcome such constraints. We specifically discuss the benefits and drawbacks of mathematical frameworks that computationally represent biological systems. Finally,we discuss the emerging discipline of synthetic biology and highlight relevant toxicologically focused applications of this technique, such as advancements in personalised medicine. We conclude this review by highlighting several opportunities and challenges that may shape the future of these rapidly evolving disciplines.

Calreticulin is an endoplasmic reticulum chaperone protein that is involved in a variety of cellular processes. It was discovered in 1974 to be a Ca2+-binding protein. Calreticulin appears to have a significant impact on the development of various cancers, and the effect of calreticulin on tumour formation and progression may vary depending on cell type and clinical stage. Calreticulin on the cell surface is thought to be a "eat-me" signal that promotes the immune system's phagocytic uptake of cancer cells. Furthermore, several studies show that manipulating calreticulin levels has a significant impact on cancer cell proliferation, angiogenesis, and differentiation. Aside from immunogenicity and tumorigenesis, interactions between calreticulin and integrins have been described during cell adhesion, which is an important process in cancer metastasis. Integrins are heterodimeric transmembrane receptors that connect the extracellular matrix to the intracellular cytoskeleton and initiate either inside-out or outside-in signalling. More and more evidence suggests that proteins binding to integrins may influence integrin-cytoskeleton interactions and thus cell adhesion ability. In this study, we reviewed the biological roles of calreticulin and summarised the potential mechanisms by which calreticulin regulates mRNA stability and thus contributes to cancer metastasis.