TY - JOUR T1 - SURVIVAL OF HUMAN MULTIPLE MYELOMA CELLS IS DEPENDENT ON MUC1-C ONCOPROTEIN FUNCTION JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.110.065011 SP - mol.110.065011 AU - Li Yin AU - Rehan Ahmad AU - Michio Kosugi AU - Turner Kufe AU - Baldev Vasir AU - David Avigan AU - Surender Kharbanda AU - Donald Kufe Y1 - 2010/05/05 UR - http://molpharm.aspetjournals.org/content/early/2010/05/05/mol.110.065011.abstract N2 - The MUC1-C oncoprotein is a direct activator of the canonical NF-κB RelA/p65 pathway and is aberrantly expressed in human multiple myeloma cells. However, it is not known if multiple myeloma cells are sensitive to disruption of MUC1-C function for survival. The present studies demonstrate that peptide inhibitors of MUC1-C oligomerization block growth of human multiple myeloma cells in vitro. Inhibition of MUC1-C function also blocked (i) the interaction between MUC1-C and NF-κB p65 and (ii) activation of the NF-κB pathway. In addition, inhibition of MUC1-C in multiple myeloma cells was associated with activation of the intrinsic apoptotic pathway and induction of late apoptosis/necrosis. Primary multiple myeloma cells, but not normal B-cells, were also sensitive to MUC1-C inhibition. Significantly, treatment of established U266 multiple myeloma xenografts growing in nude mice with a lead candidate MUC1-C inhibitor resulted in complete tumor regression and lack of recurrence. These findings indicate that multiple myeloma cells are dependent on intact MUC1-C function for constitutive activation of the canonical NF-κB pathway and for their growth and survival.The American Society for Pharmacology and Experimental Therapeutics ER -