GPR54 (KISS1R) Transactivates EGFR to Promote Breast Cancer Cell Invasiveness

Kisspeptins (Kp), peptide products of the Kisspeptin-1 (KISS1) gene are endogenous ligands for a G protein-coupled receptor 54 (GPR54). Previous findings have shown that KISS1 acts as a metastasis suppressor in numerous cancers in humans. However, recent studies have demonstrated that an increase in KISS1 and GPR54 expression in human breast tumors correlates with higher tumor grade and metastatic potential. At present, whether or not Kp signaling promotes breast cancer cell invasiveness, required for metastasis and the underlying mechanisms, is unknown. We have found that kisspeptin-10 (Kp-10), the most potent Kp, stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Matrigel-coated Transwell chamber assays and induces the formation of invasive stellate structures in three-dimensional invasion assays. Furthermore, Kp-10 stimulated an increase in matrix metalloprotease (MMP)-9 activity. We also found that Kp-10 induced the transactivation of epidermal growth factor receptor (EGFR). Knockdown of the GPCR scaffolding protein, β-arrestin 2, inhibited Kp-10-induced EGFR transactivation as well as Kp-10 induced invasion of breast cancer cells via modulation of MMP-9 secretion and activity. Finally, we found that the two receptors associate with each other under basal conditions, and FRET analysis revealed that GPR54 interacts directly with EGFR. The stability of the receptor complex formation was increased upon treatment of cells by Kp-10. Taken together, our findings suggest a novel mechanism by which Kp signaling via GPR54 stimulates breast cancer cell invasiveness

Private health insurance

The theme of work is private health insurance. First is it described in the system of health insurance and then in the territory of Czech Republic. In the work is analyzed a new draft bill of Public health insurance and systems of health insurance in the Europe. Main goal of the thessis is to find suitable privat insurance product for Czech Republic

Philaenus spumarius: when an old acquaintance becomes a new threat to European agriculture

The unique color pattern polymorphism and the foamy nymphal case of the meadow spittlebug Philaenus spumarius have attracted the attention of scientists for centuries. Nevertheless, since this species has never been considered a major threat to agriculture, biological, ecological and ethological data are missing and rather scattered. To date this knowledge has become of paramount importance, in view of the discovery of P. spumarius main role in the transmission of the bacterium Xylella fastidiosa in Italy, and possibly in other European countries. The aim of this review is to provide a state of the art about this species, with particular focus on those elements that could help developing environmental friendly and sustainable control programs to prevent transmission of X. fastidiosa. Moreover, recent findings on the role of the meadow spittlebug as vector of the fastidious bacterium within the first reported European bacterium outbreak in Apulia (South Italy) will be discussed