The mechanism by which HRG induces Taxol resistance is largely unknown. It is also known that triple negative breast cancer tumors do express high levels of HRG and unfortunately they do not respond to HRG. Our selleck chemicals studies were aimed at targeting HRG with the goal of achieving a therapeutic target as well as restoring the Nutlin-3a datasheet response to

Taxol, while preventing the formation of metastasis. Thus, we knocked-down HRG expression in three different breast cancer cell lines: MDA-MB-23, HS578T and BT549. Our data demonstrates that HRG expression is an absolute requirement for the anchorage-independent growth for triple negative breast cancer cells, since none of the breast cancer cells MDA-MB-231, HS578T and BT549 stable expressing the silencing (shRNA) for HRG, were capable of forming colony in soft agar. Furthermore, these cells, not

only no longer were not anchorage-independent were no longer resistant to Taxol, to the contrary the shRNA/HRG cells were exquisitely sensitive to Taxol, to induce growth inhibition and apoptosis. More importantly, we observed that the disorganized structured observed in 3D matrigel culture observed for triple negative cells, was completely abolished once HRG was knockdown and a very organized structure. These LY2835219 characteristics resembled an EMT (epithelial-mesenchymal epithelial transition (MET). This should be deemed a potential target in developing therapies for triple negative breast carcinomas. O23 Decoding Tumor-Host Interactions in Dormancy: Notch3-mediated Regulation of MKP-1 Promotes Tumor Cell Survival Massimo Masiero1, Sonia Minuzzo1, Irene Pusceddu2, Lidia Moserle1, Luca Persano1, Alberto Amadori1,2, Stefano Indraccolo 2 1 Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy, 2 Istituto Oncologico Veneto – IRCCS, Padova, Italy While it has been recently recognized that signals between endothelial

and cancer cells may drive escape from tumor dormancy, little is known regarding the molecular mechanisms behind science this phenomenon. Recently, we demonstrated that the Notch ligand Dll4, induced by angiogenic factors in endothelial cells, triggers Notch3 activation in neighbouring T-ALL leukaemia cells and promotes tumorigenesis. Here we show that MKP-1 levels – a broadly expressed dual specificity phosphatase – are controlled by Notch3 by a non-transcriptional mechanism involving regulation of MKP-1 protein stability. Notch3 and MKP-1 levels are consistently up-regulated in aggressive compared to dormant tumors, which is accompanied by opposite variations in the levels of active p38 and ERK1-2 – two canonical MKP-1 targets. A good correlation between Notch3 and MKP-1 levels was observed in T-ALL primary samples from patients and in a panel of T-ALL cell lines.