PYK2, a hub of signaling networks in breast cancer progression.

PYK2 functions as a signaling node and integrates multiple pathways through cross-signaling communication and feedback/forward loops, thereby modulating the amplitude and duration of signaling networks. PYK2 positively regulates the growth, epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasion of breast cancer (BC) cells, and consequently promotes breast cancer progression and metastasis. PYK2 also influences the tumor microenvironment, particularly the immune landscape, and could be a promising therapeutic target in subsets of BC patients, possibly as a combination therapy. PYK2 and its twin kinase FAK (focal adhesion kinase) contribute to BC progression through overlapping and unique functions. 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. [ABSTRACT FROM AUTHOR]