The Lysosome in Cancer: From Pathogenesis to Therapy

Dear Colleagues,

This Topical Collection of Cells collects original research and review articles addressing the role of lysosomes and of lysosomal proteins in the pathogenesis of cancer, and their possible exploitation as therapeutic targets.

The lysosome represents the final station of a network of vesicles that traffic intracellular and extracellular materials through the pathways of autophagy, phagocytosis, and endocytosis. Its subcellular localization dynamically switches from a perinuclear position near the Golgi Complex to a more peripheral position in response to metabolic signals.

Thanks to over sixty acid hydrolytic enzymes, the lysosome can degrade all the biomolecules delivered to it from inside and outside the cell, thus modeling the macromolecular composition of the cell and of the extracellular environment.

The accidental or induced release of lysosomal proteolytic enzymes (cathepsins) within the cytoplasm can trigger cell death, while their exocytosis causes the dissolution of the extracellular matrix.

Given the role in cell survival and cell death, cell homeostasis, and cell-to-cell and cell-to-extracellular environment communications, not surprisingly, lysosome positioning and function are altered in cancer cells. Failure of fusion of lysosomes with autophagosomes compromises the homeostatic and anticancer functions of autophagy. On the other hand, lysosome fusion with the plasmamembrane results in the acidification and remodeling of the extracellular matrix that is instrumental to cancer cell metastatisation.

The evidence indicates that lysosomal malfunctioning is involved in cancer pathogenesis and progression. Accordingly, lysosomal proteins in cancer may serve as diagnostic and prognostic markers, as well as therapeutic targets.

Prof. Dr. Ciro Isidoro
Prof. Dr. Marja Jäättelä
Dr. Alessandra Ferraresi
Collection Editors

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