Fig. 1

Core apoptotic signaling pathways in triple negative breast cancer (TNBC). In the extrinsic pathway, the interaction between death receptors and their ligands activates caspase 8, which then activates caspase 3, and eventually lead to apoptosis. Death receptors belong to tumor necrosis factor (TNF) receptors superfamily, which is essential for the transmission of intracellular and extracellular signals. The death receptors include FAS, TNFR1, DR4, and DR5. Death receptors bind to the corresponding proapoptotic ligand like FASL, TNF-α, and TNF-related apoptosis-inducing ligand (TRAIL), to trigger extrinsic apoptosis. In mitochondrial dependent apoptotic pathway, when DNA damage occurs, the pro-apoptotic proteins of the Bcl-2 family (such as Bax and Bak) will be upregulated and activated. Anti-apoptotic proteins (such as Bcl-2 and Bcl-xl) inhibits the action of Bax and Bak. A series of apoptogenic factors will be released into the cytosol, including cytochrome c, apaf-1, and procaspase 9, which forms a complex called apoptosome. This complex can activate caspase 9 followed by the transformation of pro-caspase 3 to caspase 3 and thus trigger apoptosis. When cells receive extracellular stimulation, they transmit the signal to inhibitor of kappa-B kinase (IKK), and inhibitor of IκB is separated from the trimer complex formed with NF-κB. The released NF-κB rapidly enters the nucleus and binds to specific sequences on deoxyribonucleic acid (DNA) to participate in physiological processes such as anti-apoptotic effects. Besides, apoptosis can also be induced by regulating the expression of p53 protein. Abbreviations: Apaf-1: Apoptotic protease activating factor 1; Bcl-2: B-cell lymphoma 2; Bcl-xl: B-cell lymphoma-extra large; DR4/5: Death receptor 4/5; FADD: Fas/fas associated via death domain; IκBα: Nuclear factor kappa-B inhibitor α; NF-κB: Nuclear factor kappa-B; RIP: Receptor-interacting protein; STAT3: Signal transducer and activator of transcription 3; TNF-α: Tumor necrosis factor-α; TNFR1: tumor necrosis factor receptor1; TRADD: TNFRSF1A associated via death domain; TRAF2: TNF receptor-associated factor 2; TRAIL: TNF-related apoptosis-inducing ligand