Sirvent Audrey, Espie Kevin, Papadopoulou Evangelia, Naim Dana, Roche Serge
Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), Centre National de la Recherche Scientifique (CNRS), Univ. Montpellier, Montpellier, France.
Front Oncol. 2022 Jul 22;12:956926. doi: 10.3389/fonc.2022.956926. eCollection 2022.
The tumor microenvironment facilitates cancer progression and therapeutic resistance. Tumor collagens and their architecture play an essential role in this process. However, little is known about the mechanisms by which tumor cells sense and respond to this extracellular matrix environment. Recently, the Discoidin Domain Receptor 1 (DDR1), a collagen receptor and tyrosine kinase has emerged as an important player in this malignant process, although the underlying signaling mechanisms remain unclear. Here, we review new DDR1 functions in tumor dormancy following dissemination, immune exclusion and therapeutic resistance induced by stromal collagens deposition. We also discuss the signaling mechanisms behind these tumor activities and the therapeutic strategies aiming at targeting these collagens-dependent tumor responses.
肿瘤微环境促进癌症进展和治疗抵抗。肿瘤胶原蛋白及其结构在此过程中起着至关重要的作用。然而，关于肿瘤细胞感知并响应这种细胞外基质环境的机制，我们知之甚少。最近，盘状结构域受体1（DDR1），一种胶原蛋白受体和酪氨酸激酶，已成为这一恶性过程中的重要参与者，尽管其潜在的信号传导机制仍不清楚。在这里，我们综述了DDR1在肿瘤播散后的休眠、免疫排斥以及由基质胶原蛋白沉积诱导的治疗抵抗中的新功能。我们还讨论了这些肿瘤活动背后的信号传导机制以及针对这些依赖胶原蛋白的肿瘤反应的治疗策略。
