Most often when we visualise the cell, we over-simplify it, but that indeed is far from reality. The cell is a highly intricate structure containing a milieu of membrane bound organelles and complex biomolecules and yes, they contain highways too! Two scientists – Raffaele Matteoni and Thomas E. Kreis in 1978, using immunofluorescence and in vivo video enhanced fluorescence microscopy, showed that lysosomes cluster around the microtubule organizing centre (MTOC) which is juxta nuclear (1). This clustering is dependent on the microtubules, as when the microtubules were depolymerized using specific agents, the lysosomes appeared dispersed throughout the cytoplasm. When the agent was removed, the lysosomes appeared to move along the microtubules, using them as highways to reorganize themselves around the MTOC.
Why are we talking about this? In the eternal pursuit to understand how cancer cells metastasize, this movement of the lysosomes has gained special importance. Most of you might be familiar with the functioning of the lysosome. Initially described by Christian de Duve in 1950 as a membrane bound organelle packed with hydrolases, we now know how this organelle is the central recycling unit of the cell, facilitating endocytosis, exocytosis, phagocytosis and autophagy. So how do these acidic bags facilitate metastasis? Studies now show that metastatic cells have significantly higher number of lysosomes at the periphery of the cell when compared to the normal cells, where they are clustered around the MTOC. These lysosomes release their proteolytic contents into the surrounding stroma of cell, thereby causing proteolytic degradation. This degradation of the surround stroma, helps the otherwise stationary cancer cell, move and make its way to its destination metastatic organ (2, 3).
Research groups are now trying to answer a few fundamental questions:
- What causes this increased peripheral localization of the lysosomes?
- How do the lysosomes travel along the microtubules?
If we find answers to this, it might be possible for us to specifically prevent this peripheral movement of the lysosomes in cancer cells and reduce chance of metastasis.
- 1.R. Matteoni, T. Kreis, Translocation and clustering of endosomes and lysosomes depends on microtubules. J Cell Biol. 105, 1253–65 (1987).
- 2.B. Rafn, C. Nielsen, S. Andersen, P. Szyniarowski, E. Corcelle-Termeau, E. Valo, N. Fehrenbacher, C. Olsen, M. Daugaard, C. Egebjerg, T. Bøttzauw, P. Kohonen, J. Nylandsted, S. Hautaniemi, J. Moreira, M. Jäättelä, T. Kallunki, ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. Mol Cell. 45, 764–76 (2012).
- 3.S. Hämälistö, M. Jäättelä, Lysosomes in cancer-living on the edge (of the cell). Curr Opin Cell Biol. 39, 69–76 (2016).