fig4

Figure 4. Apoptosis signaling pathways. Overview of the intrinsic (mitochondrial), extrinsic or death receptor (DR), and ER-stress (ERS)-mediated apoptosis pathways in response to the molecular action of anticancer agents, as well as the TRADD/NF-κB survival pathway, the growth factor (GF) receptors, and PI3K/Akt prosurvival signaling axis in CSCs. FADD: Fas-associated death domain; c-FLIP: cellular FLICE-like inhibitory protein; TRAF: tumor necrosis factor receptor associated factor; NF-κB: nuclear factor kappa B; IkB: inhibitor kappa B; IKK: inhibitor kappa B kinase; XIAP: X-linked inhibitor of apoptosis; Apaf-1: apoptotic Protease Activating Factor-1; Cyt. C: cytochrome c; PI3kinase: phosphoinositide 3-kinase; AKT: protein kinase B (PKB); PUMA: p53upregulated modulator of apoptosis; Bcl-2: B cell Lymphoma 2; Bax: Bcl-2-associated X protein; BID: BH3 interacting domain death agonist; Mcl-1: myeloid cell leukemia sequence 1; Bak: BCL-2-anatagonist/killer1; CHOP: C/EBP homologous protein; Noxa: encodes a Bcl-2 homology 3 (BH3) member of the Bcl-2 family of proteins; ATF: activating transcription factor; ER: endoplasmic reticulum; PERK: endoplasmic reticulum stress kinase; IRE1: inositol-requiring enzyme 1; RYR: ryanodine receptors Ca2+ release channels; IP3R: inositol 1,4,5-trisphosphate (IP3) regulated channels; BIP: binding immunoglobulin protein.