Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 312-326 |
| Number of pages | 15 |
| Journal | Trends in Cell Biology |
| Volume | 34 |
| Issue number | 4 |
| Early online date | 15 Aug 2023 |
| DOIs | |
| State | Published - Apr 2024 |
Bibliographical note
Publisher Copyright:© 2023 Elsevier Ltd
Funding
This work is funded by the Israel Science Foundation (grant 2142/21 ) and the Israel Cancer Research Fund (grant 20-101-PG ) (to H.G-H.), by the Agence Nationale de la Recherche (grant ANR-19-CE16-0020 ) and the Fondation pour la Recherche Médicale (grant FRM EQU201903007844 ) (to J-A.G.), and by a grant from the Israel Science Foundation (grant 1564/23 ), by a Weizmann–Pasteur collaborative grant, and a research grant from the Erica Drake Fund (to S.L.).
| Funders | Funder number |
|---|---|
| Israel Cancer Research Fund | 20-101-PG |
| Agence Nationale de la Recherche | ANR-19-CE16-0020 |
| Fondation pour la Recherche Médicale | FRM EQU201903007844, 1564/23 |
| Israel Science Foundation | 2142/21 |
Keywords
- FAK
- PYK2
- breast cancer
- feedback/feedforward loops
- signaling
- tyrosine kinase
