Figure 7.

Autophagy stimulation and inhibition in cancer cells. During tumor development, autophagy inhibition, by targeting autophagy-related proteins, such as ATG7, Beclin-1, p62/SQSTM1, and DRAM1, promotes the sensitization of cancer cells to conventional anticancer treatments, such as chemotherapeutic agents, including CDDP and 5-FU. In contrast, autophagy stimulation, evidenced by overexpression of LC3II and p62/SQSTM1, and by high levels of TGF-β1, provokes cancer cell resistance to therapies (e.g., chemotherapy and radiation), development of an aggressive phenotype, and increment of migratory and invasive capacities. In this case, several autophagy inhibitors, such as CQ, HCQ, or 3-MA, can re-sensitize resistant tumors and promote tumor regression and cancer cell death. CQ, chloroquine; HCQ, hydroxychloroquine; 3-MA, 3-methyladenine; CDDP, cisplatin; 5-FU, 5- fluorouracil.