Ricerc@Sapienza

Autophagy represents a well conserved self-degradation system critical for cellular homeostasis and survival during stress conditions. In cancer, autophagy plays as ¿double-edge sword¿, in fact it can promote or suppress tumor development, by regulating drug resistance and aggressiveness.
So far, many studies have shown that cytosolic calcium (Ca2+) oscillations are involved in the regulation of autophagic signals. Several data have demonstrated that cancer cells are able to remodel their Ca2+ signalling network and that its disruption contribute to malignant phenotype development. An important role is played by transient receptor potential (TRP) channels which are responsible for ion homeostasis, and their expression has been also associated with tumour progression, metastasis, proliferation and chemoresistance. To date, little is known about their involvement in blood malignancies, especially in chronic myeloid leukaemia (CML), and in autophagy pathway as well. Programmed death ligand 1 (PD-L1) plays a crucial role in cancer, by inhibiting immune response against cancer cell, increasing chemoresistance and relapses. It has been demonstrated that autophagy inhibition prompts PD-L1 expression; moreover, PD-L1 is found to be up regulated in CML.
Therefore, the aim of this study is to investigate in myeloid leukaemia the TRP involvement in autophagy pathway, cancer stem cell and PD-L1 expression through molecular and biochemical approaches by using specific TRP ligands, or modulating TRPs specific expression, in leukemia cell lines treated with conventional drugs.