近日，美国犹他大学Trudy G. Oliver小组发现，MYC通过重新编程神经内分泌命运来驱动小细胞肺癌（SCLC）亚型的进化。该项研究成果于2020年5月30日在线发表在《癌细胞》杂志上。

Title: MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate

Author: Abbie S. Ireland, Alexi M. Micinski, David W. Kastner, Bingqian Guo, Sarah J. Wait, Kyle B. Spainhower, Christopher C. Conley, Opal S. Chen, Matthew R. Guthrie, Danny Soltero, Yi Qiao, Xiaomeng Huang, Szabolcs Tarapcsák, Siddhartha Devarakonda, Milind D. Chalishazar, Jason Gertz, Justin C. Moser, Gabor Marth, Sonam Puri, Benjamin L. Witt, Benjamin T. Spike, Trudy G. Oliver

Issue&Volume: 2020-05-30

Abstract: Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1, NEUROD1, POU2F3, or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. In neuroendocrine cells, MYC activates Notch to dedifferentiate tumor cells, promoting a temporal shift in SCLC from ASCL1+ to NEUROD1+ to YAP1+ states. MYC alternatively promotes POU2F3+ tumors from a distinct cell type. Human SCLC exhibits intratumoral subtype heterogeneity, suggesting that this dynamic evolution occurs in patient tumors. These findings suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype.

DOI: 10.1016/j.ccell.2020.05.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30218-X