The Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche en Santé (UMRS) 1270, Sorbonne Université, 75005 Paris, France.
Trends Cell Biol. 2024 Apr;34(4):312-326. doi: 10.1016/j.tcb.2023.07.006. Epub 2023 Aug 15.
Breast cancer (BC) involves complex signaling networks characterized by extensive cross-communication and feedback loops between and within multiple signaling cascades. Many of these signaling pathways are driven by genetic alterations of oncogene and/or tumor-suppressor genes and are influenced by various environmental cues. We describe unique roles of the non-receptor tyrosine kinase (NRTK) PYK2 in signaling integration and feedback looping in BC. PYK2 functions as a signaling hub in various cascades, and its involvement in positive and negative feedback loops enhances signaling robustness, modulates signaling dynamics, and contributes to BC growth, epithelial-to-mesenchymal transition (EMT), stemness, migration, invasion, and metastasis. We also discuss the potential of PYK2 as a therapeutic target in various BC subtypes.
乳腺癌（BC）涉及复杂的信号网络，其特征是多个信号级联之间和内部存在广泛的交叉通讯和反馈回路。这些信号通路中的许多是由癌基因和/或肿瘤抑制基因的遗传改变驱动的，并受到各种环境线索的影响。我们描述了非受体酪氨酸激酶（NRTK）PYK2 在 BC 信号整合和反馈循环中的独特作用。PYK2 作为各种级联中的信号枢纽，其参与正反馈和负反馈循环增强了信号的稳健性，调节了信号动力学，并有助于 BC 的生长、上皮间质转化（EMT）、干细胞特性、迁移、侵袭和转移。我们还讨论了 PYK2 作为各种 BC 亚型治疗靶点的潜力。
