Institutes of Biomedical Sciences, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Trends Cell Biol. 2024 May;34(5):406-415. doi: 10.1016/j.tcb.2023.08.003. Epub 2023 Sep 12.
In addition to immune cells and fibroblasts, the tumor microenvironment (TME) comprises an extracellular matrix (ECM) which contains collagens (COLs) whose architecture and remodeling dictate cancer development and progression. COL receptors expressed by cancer cells sense signals generated by microenvironmental alterations in COL state to regulate cell behavior and metabolism. Discoidin domain receptor 1 (DDR1) is a key sensor of COL fiber state and composition that controls tumor cell metabolism and growth, response to therapy, and patient survival. This review focuses on DDR1 to NRF2 signaling, its modulation of autophagy and macropinocytosis (MP), and its role in cancer and other diseases. Elucidating the regulation of DDR1 activity and expression under different pathophysiological conditions will facilitate the discovery of new therapeutics.
除了免疫细胞和成纤维细胞，肿瘤微环境（TME）还包括细胞外基质（ECM），其中包含胶原蛋白（COLs），COL 的结构和重塑决定了癌症的发展和进展。癌细胞表达的 COL 受体感知 COL 状态微环境改变产生的信号，以调节细胞行为和代谢。盘状结构域受体 1（DDR1）是 COL 纤维状态和组成的关键传感器，它控制肿瘤细胞代谢和生长、对治疗的反应以及患者的生存。本综述重点介绍了 DDR1 到 NRF2 信号、其对自噬和巨胞饮（MP）的调节，以及其在癌症和其他疾病中的作用。阐明不同病理生理条件下 DDR1 活性和表达的调节将有助于发现新的治疗方法。
