Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX, USA; Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Biochim Biophys Acta Mol Cell Res. 2019 Nov;1866(11):118472. doi: 10.1016/j.bbamcr.2019.04.002. Epub 2019 Apr 5.
Epithelial-mesenchymal transition (EMT) is a developmental biological process that is hijacked during tumor progression. Cadherin switching, which disrupts adherens junctions and alters cadherin-associated signaling pathways, is common during EMT. In many tumors, substantial extracellular matrix (ECM) is deposited. Collagen is the most abundant ECM constituent and it mediates specific signaling pathways by binding to integrins and discoidin domain receptors (DDRs). The interaction of the collagen receptors results in activation of signaling pathways that promote tumor progression including an induction of the cadherin switching. DDR inhibitors have demonstrated anticancer therapeutic efficacy preclinically by inhibiting the collagen signaling. Understanding how collagen signaling impacts cellular processes including EMT and cadherin switching is of great interest especially given the strong interest in stromal targeted therapies for desmoplastic cancers.
上皮-间充质转化（EMT）是一种发育生物学过程，在肿瘤进展过程中被劫持。钙黏蛋白转换是 EMT 过程中常见的现象，它破坏了黏附连接并改变了钙黏蛋白相关的信号通路。在许多肿瘤中，大量的细胞外基质（ECM）被沉积。胶原蛋白是最丰富的 ECM 成分，它通过与整合素和盘状结构域受体（DDRs）结合来介导特定的信号通路。胶原蛋白受体的相互作用导致促进肿瘤进展的信号通路的激活，包括钙黏蛋白转换的诱导。DDR 抑制剂通过抑制胶原信号在临床前已证明具有抗癌治疗效果。了解胶原信号如何影响包括 EMT 和钙黏蛋白转换在内的细胞过程非常重要，特别是鉴于对针对促结缔组织增生性癌症的基质靶向治疗有强烈的兴趣。
