Autophagy: Detection, regulation and its role in cancer and therapy response

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Abstract
Purpose: Macroautophagy is a catabolic pathway that degrades cellular components through the lysosomal machinery. Cytoplasmic components are sequestered in double-membrane autophagosomes. They fuse with lysosomes where their cargo is delivered for degradation and recycling. Autophagy acts as a survival mechanism under stress by producing energy and as an intracellular quality management system by clearing damaged organelles like mitochondria and proteins. In this review, the regulation and the role of autophagy in cancer and therapy response are discussed. Furthermore, we will summarize methods for detecting autophagy in vitro and in vivo. Conclusion: During the early and late stages of cancer development, the role of autophagy differs. In the very early stages of carcinogenesis, autophagy has an important function by reducing cancer initiating genetic instability and aberrant protein aggregates as well as promoting anti-cancer immune response. In established malignant tumors autophagy confers resistance against metabolic stress caused by nutrient deprivation and the rapid proliferation of carcinoma cells. This function of autophagy is also important for radiation and chemotherapy resistance in cancer. Our laboratory has found that Neuropilin-2-induced autophagy is a potent mediator of therapy resistance in different cancer types. Autophagy not only promotes the survival of tumor cells, but also leads to autophagic cell death. During dysfunctional apoptosis this form of cell death mainly sensitizes cancer cells for therapy such as ionizing radiation. Therefore, the functions of autophagy during cancer progression and therapy are two-sided and further research is needed to understand these in more detail.

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