Autophagy and tumorigenesis

Abstract

Autophagy, or cellular self-digestion, is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance. Nonetheless, genetic evidence supports that autophagy functions as a tumor suppressor mechanism. Hence, the precise role of autophagy during cancer progression and treatment is both tissue and context dependent. Here, we discuss our current understanding of the biological functions of autophagy during cancer development, overview how autophagy is regulated by cancer-associated signaling pathways, and review how autophagy inhibition is being exploited to improve clinical outcomes.

Figure 1. Diverse roles for autophagy in cancer progression and therapy

(A) The suppression of autophagy induces protein aggregates and the accumulation of damaged organelles, resulting in a cascade of increased oxidative stress, genome instability, and ultimately, malignant transformation. (B) Tumor cells with combined defects in apoptosis and autophagy are prone to necrosis in response to metabolic stress. Necrosis promotes inflammatory responses, notably the recruitment of macrophages, that favors primary tumor growth. (C) Autophagy promotes oncogene-induced senescence, a barrier to malignant transformation. (D) Autophagy induction promotes tumor cell survival in response to diverse stresses, including chemotherapy, metabolic stress, and anoikis, which may facilitate drug-resistance and metastasis.

Figure 2. Cancer-associated signaling pathways that regulate autophagy in mammalian cells

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