Division of Vascular Oncology and Metastasis, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Cell Tissue Res. 2020 Jan;379(1):5-12. doi: 10.1007/s00441-019-03153-0.
Tissue homeostasis is maintained by several cellular mechanisms and an imbalance may lead to diseased states. Here, the plakophilins 1, 2 and 3 operate as structural components and stabilize desmosomal cell-cell contacts. In their non-junctional states, they serve as regulators of signaling programs and control varied cellular processes that range from transcription, mRNA abundance, protein synthesis, growth, proliferation, migration to invasion and tumor development. Accordingly, mutations in plakophilins 1 and 2 lead to skin or heart diseases. Corresponding to their strong impact on tissue homeostasis, the expression of plakophilins is specifically deregulated in various cancer types and can be correlated with patients' survival. However, our understanding on how plakophilins contribute to tumor development, progression and metastasis in a given tumor is still in its infancy and further in-depth studies using patient-derived data together with in vitro data and animal models are required.
组织稳态由多种细胞机制维持，而失衡可能导致病态。在这里， plakophilins 1、2 和 3 作为结构成分发挥作用，稳定桥粒细胞-细胞接触。在它们的非连接状态下，它们作为信号程序的调节剂，控制从转录、mRNA 丰度、蛋白质合成、生长、增殖、迁移到侵袭和肿瘤发展等多种细胞过程。相应地， plakophilins 1 和 2 的突变导致皮肤或心脏疾病。 plakophilins 的表达在各种癌症类型中特异性失调，与患者的生存相关，这与它们对组织稳态的强烈影响相对应。然而，我们对 plakophilins 如何在特定肿瘤中促进肿瘤发生、进展和转移的理解仍处于起步阶段，需要使用患者来源的数据以及体外数据和动物模型进行进一步的深入研究。
