Disentangling the MYC web

That MYC is causally associated with cancer has been apparent for decades. As a retroviral transforming gene or as the target of chromosomal translocations, rearrangements, amplification, mutations, and viral insertions, disturbance of MYC regulation and/or function is one of the most common molecular lesions contributing to multistep carcinogenesis (1–5). Disordered MYC expression alters cell proliferation, cell growth, differentiation, and metabolism. How MYC provokes this panoply of cellular pathology has been debated for years. Whether MYC acts directly on a small number of downstream effectors that elicit many secondary changes or whether MYC itself directly operates on all of these processes has been controversial. The works of Menssen and Hermeking (6) in this issue of PNAS and other recent studies (6–11) point to a complex web of direct MYC targets regulating metabolic flux and information streams through normal and transformed cells. Their work indicates the need for new tools to understand how multiple signals and processes are superimposed and integrated to determine the fate of a cell.

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