DDR1 在细胞功能和疾病进展中的二分性。

Dichotomy of the function of DDR1 in cells and disease progression.

机构信息

International Center for Wound Repair and Regeneration, Tainan, Taiwan.

International Center for Wound Repair and Regeneration, Tainan, Taiwan; Department of Physiology, National Cheng Kung University, Tainan, Taiwan.

出版信息

Biochim Biophys Acta Mol Cell Res. 2019 Nov;1866(11):118473. doi: 10.1016/j.bbamcr.2019.04.003. Epub 2019 Apr 5.

DOI:10.1016/j.bbamcr.2019.04.003

PMID:30954568

Abstract

Discoidin domain receptors DDR1 and DDR2 are collagen receptor tyrosine kinases that have many roles in tissue development and disease progression. Under physiological conditions, DDR1 is predominantly expressed in epithelial cells and functions to maintain cell differentiation and tissue homeostasis. A switch in expression from DDR1 to DDR2 occurs during epithelial-to-mesenchymal transition. However, opposite effects of DDR1 are reported to be involved in the progression of cancer and fibrotic diseases. Accumulating evidence suggests that DDR1 is involved in pro-metastasis and pro-survival signals. This review summarizes the roles of DDR1 in epithelial cell differentiation, cell migration, cancer progression and tissues fibrosis and highlights how the dichotomous functions of DDR1 may relevant to different cell types and statues. Elucidation of the underlying mechanism of the dichotomous functions of DDR1 will help to develop DDR1 as a therapeutic target.

摘要

Discoidin domain receptors DDR1 和 DDR2 是胶原受体酪氨酸激酶，在组织发育和疾病进展中具有多种作用。在生理条件下，DDR1 主要在上皮细胞中表达，其功能是维持细胞分化和组织稳态。上皮细胞向间充质转化过程中，DDR1 的表达发生转换。然而，据报道，DDR1 的相反作用参与了癌症和纤维化疾病的进展。越来越多的证据表明，DDR1 参与了促转移和促存活信号。这篇综述总结了 DDR1 在上皮细胞分化、细胞迁移、癌症进展和组织纤维化中的作用，并强调了 DDR1 的双重功能如何与不同的细胞类型和状态相关。阐明 DDR1 双重功能的潜在机制将有助于将 DDR1 作为治疗靶点进行开发。