Cardiovascular-oncogenic gene crosstalk in breast cancer: Survival, prognosis and therapeutic strategies

Figure 2 Integrated gene-cytokine-signaling networks linking breast cancer and cardiovascular disease. The figure illustrates the proposed biological relationships among Janus kinase 2, titin, Tet methylcytosine dioxygenase 2, G protein-coupled receptor kinase 4, AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma, and wingless-related integration site/β-catenin, as well as their associated cytokine networks, intracellular signaling pathways, biological effects, and disease outcomes. Janus kinase 2 is linked to cytokine-mediated Janus kinase/signal transducer and activator of transcription signaling; titin to structural integrity and nuclear factor kappa B/transforming growth factor-β-small worm phenotype mothers against decapentaplegic-associated remodeling; Tet methylcytosine dioxygenase 2 to epigenetic regulation and inflammatory responses involving the NOD-, LRR- and pyrin domain-containing protein 3 inflammasome and nuclear factor kappa B; G protein-coupled receptor kinase 4 to G protein-coupled receptor-dependent mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B signaling; AMP-activated protein kinase to energy sensing and metabolic regulation; peroxisome proliferator-activated receptor gamma to lipid metabolism and anti-inflammatory signaling; and wingless-related integration site/β-catenin to cell proliferation, survival, angiogenesis, epithelial-mesenchymal transition, and fibrosis. JAK2: Janus kinase 2; TTN: Titin; TET2: Tet methylcytosine dioxygenase 2; GRK4: G protein-coupled receptor kinase 4; GPCR: G protein-coupled receptor; AMPK: AMP-activated protein kinase; PPAR-γ: Peroxisome proliferator-activated receptor gamma; Wnt: Wingless-related integration site; TNF-α: Tumor necrosis factor alpha; IL-6: Interleukin-6; IL-1β: Interleukin-1 beta; TGF-β: Transforming growth factor beta; JAK/STAT: JAK/signal transducer and activator of transcription; NF-κβ: Nuclear factor kappa B; SMAD: Small worm phenotype mothers against decapentaplegic; NLRP3: NOD-, LRR- and pyrin domain-containing protein 3; MAPK: Mitogen-activated protein kinase; ERK: Extracellular signal-regulated kinase; PI3K/AKT: Phosphoinositide 3-kinase/protein kinase B; EMT: Epithelial-mesenchymal transition.