NOTCH receptor signaling has been implicated in the development of triple-negative breast cancer tumors. DLK2 protein, a non-canonical NOTCH signaling inhibitor has previously been shown to be involved in skin cancer. In this work, we studied whether different DLK2 expression levels affected the breast cancer features of MBA-MD-231 cells. We found that higher DLK2 expression levels led to stronger NOTCH1 inhibition. Cell cycle dynamics and apoptosis were affected by DLK2 in opposite directions, depending on the levels of NOTCH1 inhibition generated by the different levels of DLK2 expression. Only a strong inhibition of NOTCH1 by DLK2 led to a decrease in cell growth. The invasive properties of these cells were also affected. Low DLK2 expression levels led to an increase in invasiveness, whereas higher DLK2 expression levels did not significantly modify MBA-MD-231’s invasive properties. These alterations were associated to changes in the expression levels of cell adhesion proteins, such as N- and E-CADHERIN. DLK2 expression levels also affected some members of other cell signaling pathways, including ERK1/2 MAPK, AKT, and rpS6 kinases. Finally, MDA-MB-231 cells expressing high DLK2 levels were unable to generate tumors in vivo in a nude mice model. Our data support an important and complex role of DLK2 protein in the control of NOTCH signaling, tumor properties and growth dynamics of triple-negative breast cancer cells.
I graduated in Pharmacy in 2000 from San Pablo CEU University (Spain). After obtaining a predoctoral fellowship, I defended my Diploma of Advanced Studies in Biochemistry and Molecular Biology at the Complutense University of Madrid and subsequently, my Doctoral Thesis on adipogenic differentiation, which obtained the highest grade, at the UCLM, Spain (2005). Within my scientific training, my stays abroad in prestigious laboratories, such as the FDA, Maryland and KMEB, Denmark, stand out. In 2008, I joined the Oncology Research Unit of the Albacete Hospital where I initiated a line of research on the study of DLK proteins in tumor processes.
Currently, I work as Assistant Professor and teach Biochemistry and Molecular Biology in the Pharmacy, Medicine and Biotechnology Degrees and I actively participate in several academic commissions (UCLM). During these years, I have directed several TFG, TFM, DEA and Doctoral Theses that have received the highest marks. I have published several articles in international journals, mainly related to the effect of DLK and NOTCH proteins in tumor growth and migration, as well as in adipogenic differentiation.