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

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

The mechanism by which NMI impacts autophagy is through GSK3b activation, which inhibits mechanistic target of rapamycin (mTOR) signaling. 33 mTOR signaling functions as a sensor of macromolecular nutrient level within the cell and tightly couples regulation of autophagy to the energy state of the cell. 38 The mTOR complex 1 inhibits phosphorylation of autophagy related genes (ATGs) and therefore prevents the formation of the autophagosome. 39, 40 Cancer cell lines silenced for NMI, which became more resistant to doxorubicin and cisplatin, were sensitized through the addition of rapamycin, a potent inducer of autophagy and inhibitor of mTOR signaling. 33 The interaction of NMI with the above mentioned regulatory molecules suggests it may play an important role in apoptotic and autophagic cell death pathways. These cell death pathways are known to crosstalk extensively, thus it is pro-vocative to consider that NMI may function as a bridge between these parallel pathways. The precise role of NMI in these cell death pathways may be context-dependent, and additional details need to be elucidated.