fig2

Figure 2. Apoptosis inhibition in cancer cells. Increased Ca²⁺ influx through upregulated VGCC, TRP, and ORAI1-ORAI3 heterodimer leads to activation of CAMKII, which inhibits pro-apoptotic caspases 8 and 9. Downregulation of ORAI1 monomer and SERCA reduces [Ca²⁺]_ER. IP3R downregulation leads to decreased [Ca²⁺]_mit and hence inhibition of caspases 8 and 9. Reduced [Ca²⁺]_ER and [Ca²⁺]_mit lead to apoptosis inhibition. (red up arrow: upregulation, blue down arrow: downregulation, $$ \perp $$: inhibition). SERCA: sarco/endoplasmic reticulum Ca²⁺ ATPase; VGCC: voltage-gated Ca²⁺ channel; TRP: transient receptor potential; COMP1: cartilage oligomeric matrix protein; IP3R: inositol-1,4,5-trisphosphate receptor; VDAC: voltage-dependent anion channel; CAMKII: Ca²⁺/CaM-dependent protein kinase II; MCU: mitochondrial Ca²⁺ uniporter; PTEN: phosphatase and tensin homolog; FBXL2: F-box protein.