Abstract
Autophagy and the lysosomal system, together referred to as the autophagolysosomal system, is a cellular quality control network which maintains cellular health and homeostasis by removing cellular waste including protein aggregates, damaged organelles, and invading pathogens. As such, the autophagolysosomal system has roles in a variety of pathophysiological disorders, including cancer, neurological disorders, immune- and inflammation-related diseases, and metabolic alterations, among others. The autophagolysosomal system is controlled by TFEB, a master transcriptional regulator driving the expression of multiple genes, including autophagoly sosomal components. Importantly, Reactive Oxygen Species (ROS) production and control are key aspects of the physiopathological roles of the autophagolysosomal system, and may hold a key for synergistic therapeutic interventions. In this study, we reviewed our current knowledge on the biology and physiopathology of the autophagolysosomal system, and its potential for therapeutic intervention in cancer.
Highlights
The regulation of autophagy and the dynamics of the lysosomal system are intertwined to ensure cellular health and quality [1,2,3], and their disruption contributes to the physiopathology of several diseases, including cancer, neurodegeneration, metabolic and ageing-related disorders, and inflammatory diseases [1,4,5]
We reviewed the contributions of autophagy and the lysosomal system to cancer progression and chemoresistance, and the roles of Transcription factor EB (TFEB) therein
3. mechanistic Target of Rapamycin (mTOR) Signaling: A Key Regulatory Node Curbing Autophagy mTOR is a serine/threonine kinase which functions at the interface between nutrient sensing and different cellular processes leading to cell growth and proliferation [78]
Summary
The regulation of autophagy and the dynamics of the lysosomal system are intertwined to ensure cellular health and quality [1,2,3], and their disruption contributes to the physiopathology of several diseases, including cancer, neurodegeneration, metabolic and ageing-related disorders, and inflammatory diseases [1,4,5]. Several signaling pathways are frequently altered in cancer [16,17,18], among which autophagy regulatory networks and the lysosomal system represent prominent examples with potential therapeutic implications [19,20,21,22,23,24]. Lysosomotropic drugs such as chloroquine and hydroxychloroquine are currently being tested in the clinic [24,25,26]. We reviewed the contributions of autophagy and the lysosomal system to cancer progression and chemoresistance, and the roles of TFEB therein
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