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Oncogene (2013) 32, 19952004& 2013 Macmillan Publishers Limited All rights reserved 0950-9232/13
http://www.nature.com/ONC
Web End =www.nature.com/onc
REVIEW
Cancer-associated lysosomal changes: friends or foes?
T Kallunki, OD Olsen and M Jaattela
Rapidly dividing and invasive cancer cells are strongly dependent on effective lysosomal function. Accordingly, transformation and cancer progression are characterized by dramatic changes in lysosomal volume, composition and cellular distribution. Depending on ones point of view, the cancer-associated changes in the lysosomal compartment can be regarded as friends or foes. Most of them are clearly transforming as they promote invasive growth, angiogenesis and drug resistance. The same changes can, however, strongly sensitize cells to lysosomal membrane permeabilization and thereby to lysosome-targeting anti-cancer drugs. In this review we compile our current knowledge on cancer-associated changes in lysosomal composition and discuss the consequences of these alterations to cancer progression and the possibilities they can bring to cancer therapy.
Oncogene (2013) 32, 19952004; doi:http://dx.doi.org/10.1038/onc.2012.292
Web End =10.1038/onc.2012.292 ; published online 9 July 2012
Keywords: Lysosome; Cancer; metastasis; cell death
INTRODUCTIONLysosomes are acidic (pH 4.55) catabolic organelles found in all mammalian cells except for mature erythrocytes. They are responsible for the disposal and recycling of worn out and damaged cellular macromolecules and organelles as well as the digestion of extracellular and foreign materials delivered to them by endocytosis, autophagy and phagocytosis13 (Figure 1). The digestion of the cargo is brought about by hydrolases residing in the lysosomal lumen, and the products are recycled back to the cytosol via diffusion and specic transport channels or released to the extracellular space by exocytosis.
Malignant transformation introduces series of changes in lysosomes and their function (Figure 1). These include increased lysosomal biogenesis and hydrolase activity, changes in the lysosomal membrane composition and enhanced secretion of lysosomal contents to the extracellular space.47 Accordingly, increases in the expression and function of various lysosomal hydrolases are common in human tumors, and they often correlate with a higher risk of recurrence and poor prognosis.810 In addition to their possible use as prognostic biomarkers, mounting evidence points to essential roles for extracellular lysosomal enzymes in cancer invasiveness, angiogenesis and progression, making these enzymes attractive targets for cancer therapy.5,10 By contrast,
intracellular release of lysosomal hydrolases can trigger apoptosis or non-apoptotic lysosomal cell death providing a rational for...