Roles of N-Myc and STAT interactor in cancer: From initiation to dissemination

Pruitt, Hawley C.; Devine, Daniel J.; Samant, Rajeev S.

NMI was identified through its interaction with Myc family members N-myc and c-Myc, as well as their dimerization partner, Max. 1 Both members of the Myc family promote cell division and growth in different cancer types. N-myc is most notable in neuroblastoma, where 20% of tumors exhibit amplification of the N-myc gene. 21 Similarly, c-Myc expression is high in a wide array of cancers, including breast cancer. 22 The interaction between NMI and Myc family members was confirmed in non-cancerous cell lines and repeatedly observed in breast cancer cells, as mentioned previously. c-Myc is able to influence all steps of cancer initiation and progression, perhaps due to its wide array of target genes and effects on multiple RNA polymerases. 23, 24 c-Myc is a relatively weak transcription factor with the ability to activate or repress transcription in a context-dependent manner and depending on its transcription co-factor influence. 25 However, a c-Myc core signature of target genes reveals that transcripts regulated by c-Myc promote cellular biomass accumulation as well as cell division through up-regulation of genes involved in ribosome biogenesis and cell cycle advancement, respectively. 26 It is not known whether the interaction between NMI and c-Myc alters transcription or how NMI binding would change the expression of specific c-Myc transcriptional targets. c-Myc contributes to multiple aspects of carcinogenesis. Hence, the potential role of NMI regulating c-Myc-mediated transcription could provide potential targets in developing novel cancer therapeutics.