除了免疫细胞和成纤维细胞外，肿瘤微环境(TME)还包括包含胶原蛋白(COLs)的细胞外基质(ECM)，其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。圆盘蜘蛛蛋白结构域受体1 (DDR1)是COL纤维状态和组成的关键传感器，它控制肿瘤细胞的代谢和生长、对治疗的反应以及患者的生存。本综述聚焦于DDR1到NRF2信号传导，其对自噬和巨噬作用的调节，以及在癌症和其他疾病中的作用。阐明DDR1在不同病理生理条件下的活性和表达调控将有助于新疗法的发现。版权所有© 2023 Elsevier Ltd. 保留所有权利。

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.Copyright © 2023 Elsevier Ltd. All rights reserved.