Signaling pathway dysregulation in breast cancer (IMAGE)
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Figure 1: Key signaling pathways and targeted factors in dysregulated BC. This figure illustrates the major signaling pathways and their intricate crosstalk in BC, focusing on the GPCR, RTKs, RAS/RAF/MEK1/2/ERK1/2, MAPK, HER2, PI3K/Akt/mTOR, Wnt/β-catenin, NF-κB, Notch, and DDR pathways. These pathways are critical in regulating essential cellular processes such as proliferation, survival, differentiation, and metastasis. The MAPK pathway, initiated by RTKs like EGFR and HER2, activates downstream effectors such as RAS, RAF, MEK, and ERK1/2, driving cell growth and survival. HER2 amplification further drives oncogenesis by activating the MAPK and PI3K/Akt pathways, with HER3 and HER4 modulating these signals. The PI3K/Akt/mTOR pathway controls cell growth and metabolism through Akt activation and downstream targets like mTORC1/2, p70S6K1, and 4E-BP1. Mutations in PIK3CA and loss of PTEN contribute to its hyperactivation. The Wnt/β-catenin pathway promotes EMT and metastasis, driven by Wnt signaling through LRP5/6 and β-catenin, which interact with APC, CKIα, and TCF/LEF. The NF-κB pathway is a central signaling network regulating inflammation, immune responses, and cell survival. This pathway is activated through Tumor Necrosis Factor Receptors (TNFR), Toll-like Receptors (TLRs), and the IκB kinase (IKK) complex. The Notch pathway, triggered by receptor-ligand interactions between Notch receptors and ligands like DLL, governs cell fate determination and contributes to cancer progression by promoting proliferation and maintaining cancer stem cells. The DDR pathway is essential for maintaining genomic stability by detecting and repairing DNA damage. It responds to various types of damage, including DSBs, SSBs, and cross-links, by activating repair mechanisms such as HR for DSBs and NER to other kinds of damage. In BC, dysregulation of the DDR pathway, often due to mutations in genes like BRCA1 and BRCA2, impairs DNA repair, leading to genomic instability and an increased risk of cancer.
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Copyright: © 2025 Ryspayeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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