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. 2023 Dec 12;14(5):100919. doi: 10.1016/j.jpha.2023.12.009

Fig. 4.

Fig. 4

Molecular signaling pathway for nitrosamines in various types of cancers. (i) Lung cancer: nitrosamines can stimulate proliferation, migration and cancer cell survival by modulating G-protein signaling, nAchR signaling, and EGFR signaling. (ii) Breast cancer: nitrosamines modulates adenylyl cyclase/cAMP/PKA/CREB pathway, which mediates EGFR signaling pathway transactivation. (iii) Hepatic cancer: N-nitrosamines exposure affects hepatic lipid metabolism through the alteration of mitochondrial DNA, OXPHOS signaling, and other mitochondrial metabolic pathways. I: nicotinamide adenine dinucleotide (NADH)-ubiquinone oxidoreductase complex; II: succinic acid-ubiquinone oxidoreductase complex; III: cytochrome Bc1 complex; IV: cytochrome C oxidase complex; and V: adenosine triphosphate synthase complex; B-AR: β-adrenergic receptor; Adr: adrenaline; NAdr: noradrenaline; HIF1α: hypoxia inducible factor 1α; VEGF: protein kinase B; RAF: rapidly accelerated fibrosarcoma; PKC: protein kinase C; ERK: extracellular signal-regulated kinase; MEK: mitogen‑activated protein kinase kinase; RAP-1: Ras-related protein 1; BAD:  BCL2 associated agonist of cell death protein mTor: mammalian target of rapamycin; PI3K: phosphoinositide 3-kinase; VGCC: voltage gated calcium channel; nAchR: nicotinic acetylcholine receptors; CREB: cAMP response element-binding protein; FOS, JUN and Myc: transcription factors; μ-m calpain: isozymes of calpain; FOXO: forkhead transcription factor; GSK3: glycogen synthase kinase 3; TSC2: tuberous sclerosis 2; ASK1: apoptosis signal-regulating kinase 1; 4EBP1: eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1; S6K1: S6 kinase 1; PLA2: phospholipase-A2; PKA: protein kinase A; TxA2: thromboxane A2; SREBP-1: sterol regulatory element-binding protein 1; CREM: cAMP Response Element Modulating protein; NF-kB: nuclear factor kappa B; Bcl2: B cell lymphoma 2; HO-1: heme oxygenase-1; AA: arachidonic acid; RAS: rat sarcoma proteins; STAT: signal transducer and activator of transcription; AP1: activator protein 1; PI3K: phosphoinositide 3-kinase; MAPK: mitogen-activated protein kinase; VDR: vitamin D receptor; FASN: fatty acid synthase; ROS: reactive oxygen species; CD36: fatty acid translocase; SOD: superoxide dismutase; ACC: acetyl-CoA carboxylase; TNF-α: tumor necrosis factor alpha; IL-1β: interleukin-1β; SCD: stearoyl-CoA desaturase; ELOVL1: ELOVL fatty acid elongase 1; ACBP: acyl-CoA binding protein, TAG: triacylglycerols; DAG: diacylglycerols; PA: phosphatidic acids; CPT1: carnitine palmitoyltransferase 1; GSH: glutathione; GSSG: glutathione disulfide; MDA: malondialdehyde; NAD: nicotinamide adenine dinucleotide; TFAM: mitochondrial transcription factor-A.