Endosomes, lysosomes, and the role of endosomal and lysosomal biogenesis in cancer development
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REVIEW
Endosomes, lysosomes, and the role of endosomal and lysosomal biogenesis in cancer development Jonathan L. Jeger1 Received: 16 September 2020 / Revised: 2 November 2020 / Accepted: 6 November 2020 © Springer Nature B.V. 2020
Abstract Endosomes and lysosomes are membrane-bound organelles crucial for the normal functioning of the eukaryotic cell. The primary function of endosomes relates to the transportation of extracellular material into the intracellular domain. Lysosomes, on the other hand, are primarily involved in the degradation of macromolecules. Endosomes and lysosomes interact through two distinct pathways: kiss-and-run and direct fusion. In addition to the internalization of particles, endosomes also play an important role in cell signaling and autophagy. Disruptions in either of these processes may contribute to cancer development. Lysosomal proteins, such as cathepsins, can play a role in both tumorigenesis and cancer cell apoptosis. Since endosomal and lysosomal biogenesis and signaling are important components of normal cellular growth and proliferation, proteins involved in these processes are attractive targets for cancer research and, potentially, therapeutics. This literature review provides an overview of the endocytic pathway, endolysosome formation, and the interplay between endosomal/ lysosomal biogenesis and carcinogenesis. Keywords Endosomes · Lysosomes · Endocytosis · Cathepsins · Carcinogenesis
Background Endosomes and endocytosis Endosomes are membrane-bound organelles which act as temporary transportation vesicles in the passage of substances into and out of a eukaryotic cell [1]. The cell’s plasma membrane (PM) is a dynamic structure that prevents unregulated exchange of biomolecules between the intracellular and extracellular compartments. Smaller molecules, including sugars and ions, can utilize integral membrane proteins, such as channels and pumps, to cross the PM. Macromolecules, on the other hand, need to be internalized by primary endocytic vesicles (PEVs) formed by invaginations of the cell’s PM [2]. These vesicles deliver their contents to early endosomes (EEs) in the peripheral cytoplasm [3]. The uptake and transportation of extracellular material through the formation of membrane-bound vesicles can occur through a variety of different pathways, collectively known
* Jonathan L. Jeger [email protected] 1
School of Medicine, Trinity College Dublin, Dublin, Ireland
as endocytosis [2, 4]. The various pathways through which macromolecules cross the PM can be differentiated based on the size of the endocytosed particles and the size of the invaginations they form. Micropinocytosis refers to invaginations 500 nm, such as bacterial pathogens and apoptotic cell debris, are usually internalized through a process known as phagocytosis, which takes place in specialized cells of the innate immune system [2, 10]. Macrophages, for example, utilize various phagocytic receptors to recognize and internalize pathogenic particles [11, 12]. Following internalization, the PM-derived i
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