Lysosomes in cancer—living on the edge (of the cell)

Abstract

The lysosomes have definitely polished their status inside the cell. Being discovered as the last resort of discarded cellular biomass, the steady rising of this versatile signaling organelle is currently ongoing. This review discusses the recent data on the unconventional functions of lysosomes, focusing mainly on the less studied lysosomes residing in the cellular periphery. We emphasize our discussion on the emerging paths the lysosomes have taken in promoting cancer progression to metastatic disease. Finally, we address how the altered cancerous lysosomes in metastatic cancers may be specifically targeted and what are the pending questions awaiting for elucidation.

Single organelle dynamics linked to 3D structure by correlative live‐cell imaging and 3D electron microscopy

“…It is becoming increasingly clear that endolysosomal trafficking, positioning and organelle interaction are important parameters for lysosomal maturation, membrane interactions and functioning . Moreover, defective regulation of endosomal trafficking is seen in many neurological disorders, like Huntington's disease, Alzheimer and Charcot‐Marie‐Tooth type 2B, and subpopulations of lysosomes are linked to axon formation and cancer progression . To be able to understand the function and regulation of these dynamic interactions it is required that ultrastructural and molecular characteristics are directly linked to parameters that can only be derived from live cells, such as organelle dynamics, positioning and enzyme activities.…”

“…Charcot-Marie-Tooth type 2B, 72,86,87 and subpopulations of lysosomes are linked to axon formation and cancer progression. 88,89 To be able to understand the function and regulation of these dynamic interactions it is required that ultrastructural and molecular characteristics are directly linked to parameters that can only be derived from live cells, such as organelle dynamics, positioning and enzyme activities. Since our approach integrates information on the dynamics, molecular composition and ultrastructural context of a single compartment, it is highly suited for multiparameter examination of individual organelles, in healthy and diseased states.…”

Lysosomal Biology in Cancer

“…For example, cells can expel ATP to the extracellular space with this secretory pathway to mediate cellular signaling through ATP receptors [38, 39]. The observation that lysosomal exocytosis can play a role in cell signaling, proteolytic extracellular matrix (ECM) remodeling and tumor invasion suggests that targeting lysosomal exocytosis rather than individual cathepsins would be a more promising strategy [40]. …”

Cathepsins in digestive cancers

“…The relationship between cathepsins and tumors has been studied for approximately 40 years [8]. Various cathepsins contribute to extracellular matrix (ECM) degradation and remodeling in the tumor microenvironment [9, 10], resulting in the acceleration of tumor progression and invasion [11–16]. In general, a higher level of cathepsins is associated with a poorer prognosis [17–19].…”