Elena embarked on her doctoral project journey in the beginning of 2020, together with other 15 PhD students, as part of a doctoral training network focusing on uncovering the role of the secretory pathway in disease, specifically in cancer. The network was funded by the European Union through its Marie Skłodowska-Curie Actions Horizon 2020 program. On the 11th of October, Elena defended her work in front of her colleagues and the thesis committee members, obtaining her degree with a "magna cum laude" distinction!
The project - Digging deeper into the link between the kinase PKD and stemness
The Protein Kinase D (PKD) family (comprising PKD1, PKD2 and PKD3), is involved in various cellular processes including proliferation, protein transport, migration, secretion and stress response. Previous studies demonstrated that the members of the PKD family are mainly located at the trans-Golgi network, which, together with the highly conserved structure within the three isoforms, suggests isoform redundancy.
However, an isoform-specific dysregulation of PKD expression has been found in different tumors, including breast cancer. While PKD1 and PKD2 are the main isoforms in normal tissue and non-invasive breast cancers, the PKD3 isoform is overexpressed in triple-negative breast cancer (TNBC), in which PKD1 is epigenetically silenced, suggesting isoform-specific functions. In particular, in TNBC PKD3 was shown to be necessary to maintain the stem cell population, as well as to support cell proliferation via preserving the integrity of the endolysosomal compartment.
Elena's PhD work was uncovering the underlying mechanism regulating PKD3 function, including the discovery of a previously unrecognized role for PKD3 at the additional compartments of the secretory pathway, providing new insights into the isoform-specific functions of the PKD family in TNBC cells. Finally, her work also postulates a potential PKD3 substrate at this compartment, in pursuit of a specific mechanism which could explain the observed PKD3- dependent effects on cellular secretion.
We are eagerly looking forward to the publication that will detail all this hard work!