Autophagy in cellular metabolism and cancer

Jiang, Xuejun; Overholtzer, Michael; Thompson, Craig B.

doi:10.1172/jci73942

Cited by 180 publications

(149 citation statements)

References 129 publications

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“…Autophagy can be activated when cells encounter stresses such as nutrient starvation, hypoxia, as well as a wide range of anticancer therapies. For this reason, combination of autophagy inhibition and other cancer treatments might be an effective anticancer therapeutic approach [19]. On the other hand, autophagy may also be a cell death mechanism under certain specific contexts -the so-called 'autophagic cell death', via less defined mechanisms [20,32].…”

Section: Discussionmentioning

confidence: 99%

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Ferroptosis is an autophagic cell death process

et al. 2016

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Ferroptosis is an iron-dependent form of regulated necrosis. It is implicated in various human diseases, including ischemic organ damage and cancer. Here, we report the crucial role of autophagy, particularly autophagic degradation of cellular iron storage proteins (a process known as ferritinophagy), in ferroptosis. Using RNAi screening coupled with subsequent genetic analysis, we identified multiple autophagy-related genes as positive regulators of ferroptosis. Ferroptosis induction led to autophagy activation and consequent degradation of ferritin and ferritinophagy cargo receptor NCOA4. Consistently, inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4 abrogated the accumulation of ferroptosis-associated cellular labile iron and reactive oxygen species, as well as eventual ferroptotic cell death. Therefore, ferroptosis is an autophagic cell death process, and NCOA4-mediated ferritinophagy supports ferroptosis by controlling cellular iron homeostasis.

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Section: Discussionmentioning

confidence: 99%

“…Autophagy is a conserved intracellular catabolic process that delivers cellular components to the lysosome for degradation [19]. The core machinery of autophagy consists of over 30 autophagy-related genes (ATGs).…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis is an autophagic cell death process

et al. 2016

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“…Tumor cells usually have a high proliferation rate, which demands more energy and resources than normal cells, and both ATP and metabolites can be obtained by increasing autophagy [54] . Although angiogenesis does occur in tumors, the availa bility of glucose and glutamine is reduced in some tumor regions due to the leakiness of tumorassociated vessels and continued hypovascularization [55] . Autophagy is activated in the hypoxic areas of tumors, and the inhibition of autophagy by AKT activ ation or by monoallelic disruption of BECN1 promotes cell death specifically in those regions.…”

Section: Autophagy As a Promoting Factor During Late Stagesmentioning

confidence: 99%

Autophagy in colorectal cancer: An important switch from physiology to pathology

Burada

Nicoli

Ciurea

et al. 2015

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138

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Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of Core tip: This review describes the role of autophagy in cancer, focusing on the involvement of autophagy in colorectal cancer (CRC). Initially, we describe the steps and components of autophagy, and we then further highlight the dual role of autophagy in cancer, where it can potentially act as both a promoter and an inhibitor during the transformation from normal to malignant cell. In particular, we emphasize the major autophagy genes involved in CRC pathogenesis along with autophagymodulating agents and their modes of action in the context of CRC therapy. TOPIC HIGHLIGHT

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“…65 Autophagy is primarily a prosurvival adaptive response that enables cells to tolerate unfavorable conditions, including those to which cancer cells are exposed. 16,55,[66][67][68][69][70] In response to metabolic stress, caused by limited nutrient and oxygen, autophagy is induced resulting in the degradation of some cellular components and their recycling. This provides nutrients and energy necessary to sustain metabolism; in the case of cancer cells, this ensures tumor growth and survival.…”

Section: Regulation and Role Of Autophagy In Cancer Cellsmentioning

confidence: 99%