Enigmatic MYC conducts an unfolding systems biology symphony

The enigmatic MYC oncogene, which participates broadly in cancers, revealed itself recently as the maestro of an unfolding symphony of cell growth, proliferation, death, and metabolism. The study of MYC is arguably most challenging to its students but at the same time exhilarating when MYC reveals its deeply held secrets. It is the excitement of our richer understanding of MYC that is captured in each review of this special issue of Genes & Cancer. Collectively, our deeper understanding of MYC reveals that it is a symphony conductor, controlling a large orchestra of target genes. Although MYC controls many orchestra sections, which are necessary but not sufficient for Myc function, ribosome biogenesis stands out to reveal Myc's primordial function particularly in fruit flies. Because ribosome biogenesis and the associated translational machinery are bioenergetically demanding, Myc's other target genes involved in energy metabolism must be coupled with energy demand to ensure that cells can replicate their genome and produce daughter cells. Normal cells have feedback loops that diminish MYC expression when nutrients are scarce. On the other hand, when deregulated Myc transforms cells, their constitutive bioenergetic demand can trigger cell death when energy is unavailable. This special issue captures the unfolding symphony of MYC-mediated tumorigenesis through reviews that span from a timeline of MYC research, fundamental understanding of how the MYC gene itself is regulated, the study of Myc in model organisms, Myc function, and target genes to translational research in search of new therapeutic modalities for the treatment of cancer.