Laboratory of Mucosal Exposome and Biomodulation, Department of Integrative Biomedical Sciences and Biomedical Research Institute, Pusan National University, Yangsan, Korea.
Graduate Program of Genomic Data Sciences, Pusan National University, Yangsan, Korea.
Commun Biol. 2021 May 10;4(1):543. doi: 10.1038/s42003-021-02078-1.
The majorities of colorectal cancer (CRC) cases are sporadic in origin and a large proportion of etiologies are associated with environmental stress responses. In response to external and internal stress, the ribosome stands sentinel and stress-driven ribosomal dysfunction triggers the cellular decision pathways via transcriptional reprogramming. In the present study, PR domain zinc finger protein (PRDM) 1, a master transcriptional regulator, was found to be closely associated with ribosomal actions in patients with CRC and the murine models. Stress-driven ribosomal dysfunction enhanced PRDM1 levels in intestinal cancer cells, which contributed to their survival and enhanced cancer cell stemness against cancer treatment. Mechanistically, PRDM1 facilitated clustering modulation of insulin-like growth factor (IGF) receptor-associated genes, which supported cancer cell growth and stemness-linked features. Ribosomal dysfunction-responsive PRDM1 facilitated signaling remodeling for the survival of tumor progenitors, providing compelling evidence for the progression of sporadic CRC.
大多数结直肠癌（CRC）病例是散发性的，很大一部分病因与环境应激反应有关。核糖体作为哨兵，对外界和内部的应激做出反应，应激驱动的核糖体功能障碍通过转录重编程触发细胞决策途径。在本研究中，发现 PR 结构域锌指蛋白（PRDM）1 作为一个主要的转录调控因子，与 CRC 患者和小鼠模型中的核糖体作用密切相关。应激驱动的核糖体功能障碍增加了肠道癌细胞中 PRDM1 的水平，这有助于它们的存活，并增强了癌细胞对癌症治疗的干性。从机制上讲，PRDM1 促进了胰岛素样生长因子（IGF）受体相关基因的簇调节，从而支持癌细胞的生长和干性相关特征。核糖体功能障碍反应性 PRDM1 促进了信号转导重塑，以维持肿瘤前体的存活，为散发性 CRC 的进展提供了有力的证据。
