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Myc pathways provoking cell suicide and cancer

Abstract

A paradox for the cancer biology field has been the revelation that oncogenes, once thought to simply provide advantages to a cancer cell, actually put it at dire risk of cell suicide. Myc is the quintessential oncogene in this respect, as in normal cells it is required for cell cycle traverse, whereas in cancers it is overexpressed and functions as the angiogenic switch. Nonetheless, Myc overexpression kills normal cells dead in their tracks. Here we review Myc-induced pathways that contribute to the apoptotic response. Molecular analysis of Myc-induced tumors has established that some of these apoptotic pathways are essential checkpoints that guard the cell from cancer, as they are selectively bypassed during tumorigenesis. The precise mechanism(s) by which Myc targets these pathways are largely unresolved, but we propose that they involve crosstalk and feedback regulatory loops between arbiters of cell death.

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Acknowledgements

We thank current and past members of the laboratory for their efforts, dedication and insights into Myc, cell suicide and cancer. We are also deeply indebted to the Roussel-Sherr, Zambetti and Ihle laboratories for our exciting and productive collaborations over the past decade. We apologize for any omissions of work from our colleagues relevant to the problem, as tackling Myc and apoptosis certainly ‘takes a village’. It was simply our intent to focus the review on those pathways shown to be most relevant to cancer. Our research is supported by grants from the NIH and by the American Lebanese Syrian Associated Charities (ALSAC). JA Nilsson is a George J. Mitchell Endowed Postdoctoral Fellow of St Jude Children's Research Hospital.

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Nilsson, J., Cleveland, J. Myc pathways provoking cell suicide and cancer. Oncogene 22, 9007–9021 (2003). https://doi.org/10.1038/sj.onc.1207261

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