Ciara Himlin
Research Mentor: Ejaz Ahmad
Mentor Department: Surgery (Section-Pediatric Surgery), Medicine
Author(s): Ciara Himlin, Sahiti Chukkapalli, Erika Newman, Ejaz Ahmad
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 21
Abstract
Neuroblastoma remains a clinically heterogeneous disease, with MYCN amplification serving as a primary marker of poor prognosis. While the sympathetic nervous system significantly influences the tumor microenvironment, the intracellular signaling response to adrenergic stimulation across different MYCN statuses remains poorly defined. Here, we demonstrate that exposure to epinephrine triggers divergent signaling cascades in SH-SY5Y (MYCN non-amplified) versus Kelly (MYCN-amplified) cells. In SH-SY5Y cells, epinephrine induces robust CREB phosphorylation at S133 while suppressing the Akt/GSK3ß axis. Conversely, MYCN-amplified cells exhibit a rapid activation of the PI3K/Akt/mTOR pathway. The downregulation of Akt phosphorylation at S473 in SH-SY5Y cells suggests that epinephrine might exert an anti-proliferative effect or induce differentiation in non-aggressive backgrounds. However, the ‘switching’ of this signal to activate Akt in Kelly cells highlights a mechanism by which MYCN promotes chemoresistance and aggressive growth under physiological stress. Overall, the obtained results suggest that MYCN amplification shifts the adrenergic response from a transcriptional stress profile to an oncogenic survival signal.
