?(Fig
?(Fig.4C).4C). upregulates BLNK in human being trastuzumab-sensitive but not trastuzumab-resistant ErbB2-positive breast cancer cells. Moreover, we founded that BLNK promotes anoikis by activating p38 MAP kinase and that ErbB2-dependent BLNK downregulation blocks breast malignancy cell anoikis. In search for pharmacological methods permitting to upregulate BLNK in tumor cells we found that clinically authorized proteasome inhibitor bortezomib upregulates IRF6 and BLNK in GB110 human being breast malignancy cells and inhibits their 3D growth inside a BLNK-dependent manner. In addition, we found that BLNK upregulation in human being ErbB2-positive breast malignancy cells blocks their ability to form tumors in mice. Furthermore, we used publicly obtainable data on mRNA amounts in multiple breasts cancers to show that elevated BLNK mRNA amounts correlate with an increase of relapse-free survival within a GB110 cohort of…