**16. Future directions**

120 Cancer Prevention – From Mechanisms to Translational Benefits

These results are promising, first because they make it possible to relate the LMC disease to the presence of cytoplasmic Kaiso, and second, because the molecule may have a diagnostic

Another noteworthy aspect is that the cellular compartments are currently the object of many discussions in experimental biology, and we are witnessing a reconceptualization of these compartments, which involves the way they are structured and work, as well as their

It is logical to think that since a cell is in a process of constant division, for any given cell division, the elements in the nucleus and the cytoplasm are mixed, and at this important moment for cellular functioning, the cytoplasmic and nuclear components share the same general compartment that is the cytoplasm of the cell under division. According to this view, there is a very tenuous separation between the cytoplasm and the nucleus of a cell, and the sub compartments generated inside the cytoplasm are what really matters in a cell. Although many scenarios of the separation of specific functions have been detected inside the nucleus (Zhao et al., 2009; Spector & Lamond, 2011), none of these microenvironments

These new sub compartments that are important for the understanding of the mechanisms of diseases such as cancer are the networks of endocytic membrane represented by a system of interconnected membranous organelles and endosomes that are responsible for the selection of destination and transport of various types of macromolecules from the extracellular milieu into the cell and within the cell. A recent discovery reveals that the process of endocytosis and endosomes would be crucial for the maintenance of cellular homeostasis, ensuring the compartmentalization of transduction processes of intracellular signals (Scita & Di Fiore, 2010). It is now widely accepted that systems of endocytic membrane trafficking and intracellular signaling are closely interconnected and endosomes

The main endosomal compartment that regulates intracellular signaling processes would be the so-called multivesicular bodies (MVB). It would have a specific role in the sequestration of receptors activated in the membrane that by means of an intracellular mechanism of endocytosis would be placed inside the lumen of the MVB, unable to access the components of intracellular signaling, which would reduce and negatively regulate the signaling

Surprisingly, this compartment can also play a role in positive regulation of certain signaling pathways through sequestration of inhibitors (Taelman et al., 2010). Because of its important role in cancer, it is worth mentioning that the Gsk3 and CK1 promoted by the Wnt signaling pathways would be hidden in internal vesicles inside the MVB. The protein complexes involving the Wnt receptor, Gsk3 and CK1 (among others), are then taken inside the lumen of the MVB, separating Gsk3 from their cytoplasmic substrates (Figure 1h). Consequently, in the absence of Gsk3, which is now inside the MVB, β-catenin would be

The endosomal compartments are, thus, a trapping mechanism of enzyme and receptors, and it is believed that it produces the stabilization of many cellular proteins. Coincidentally,

value of clinical interest, not only in LMC, but also in other types of leukemia.

possible relationships with disease development at the cellular level.

would be maintained in cells in the process of cell division.

could act as signaling platforms (Hupalowska & Miaczynska, 2011).

pathway of these receptors (Katzmann et al., 2002; Raiborg & Stenmark, 2009).

stabilized in the cytoplasm, translocate into the nucleus and activate transcription.

**15. The new view of cellular compartments** 

Therefore, a view focused on subcellular compartments and proteins modulating the epigenome can provide a greater understanding of the biology of malignant cells, as well as improve our approach to cancer treatment. It is known that cancer treatment is dictated by the stage of the disease, and that cancer treatment is more effective during the chronic phase of the disease. Unfortunately, clinical and molecular tests cannot predict disease progression, which can create an obstacle to diagnosis: the inability to identify subtypes of patients most likely to benefit from specific treatment options for specific stages of the disease, which would make it possible to offer a therapy targeted to a given cancer patient.

Finally, the understanding of this new biology of disease progression can provide markers for clinical diagnosis and different approximations for better therapeutic strategies. Also, there is always hope that we'll be able to identify proteins and signaling pathways that may be useful as reliable prognostic markers of the disease and therapeutic targets in the near future.
