fig3

Figure 3. 5-FU Resistance develops from an altered balance between autophagy, which favors cell survival and apoptosis in 5-FU-treated cells. p53 is a key regulator of autophagy/apoptosis balance in 5-FU-treated cells and is modulated by SHMT2. Increased signaling through the PI3K/Akt/mTOR pathway stimulates LC3II and upregulates autophagy to promote cell survival and 5-FU resistance. Induction of apoptosis involves upregulation of the death receptor pathway or mitochondrial pathway for programmed cell death, and downregulation of Fas/FasL or Bax/Bak decreases 5-FU-induced apoptosis and promotes cell survival and 5-FU resistance. 5-FU: 5-Fluorouracil; TS: thymidylate synthase; FdUMP: 5-Fluoro-2’-deoxyuridine-5’-O-monophosphate; FdUTP: 5-fluoro-2′-deoxyuridine-5′-triphosphate; SHMT2: serine hydroxymethyl transferase.