Abstract 1592: Pulsatile Myc expression as a source of Myc heterogeneity in cancer cells

Abstract

Abstract Myc is the most commonly amplified oncogene, and is known to play critical roles in cancer establishment and maintenance. Myc expression heterogeneity has also been linked to cancer drug resistance; however, the source of this heterogeneity remains poorly characterized. Even in isogenic cancer cell lines, we found that Myc is one of the most heterogeneously expressed transcription factors at the single-cell level. This heterogeneity is independent of cell cycle progression, local cell density, and p53/p21 signaling. To elucidate the source and duration of Myc heterogeneity, we endogenously tagged Myc with a fluorescent protein and used long-term live-cell imaging techniques to monitor Myc expression over time at single-cell resolution. Surprisingly, we found that Myc expression is pulsatile, explaining why Myc expression appears heterogeneous at a given point in time. Furthermore, we found that Myc dynamics are heterogeneous, and the dynamics are not always heritable. Additionally, Myc pulse amplitude is correlated with the duration of G1 and the overall cell cycle, suggesting that the pulses may be a mechanism for escaping many chemotherapy agents. Finally, we show that Myc pulses are primarily transcription-driven and controlled by at least one negative feedback loop. Our findings demonstrate for the first time that Myc expression is pulsatile, and provide insights into Myc regulation in cancer. Citation Format: Chad Liu, Karen Gascoigne. Pulsatile Myc expression as a source of Myc heterogeneity in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1592.