PT  - JOURNAL ARTICLE
AU  - Li Yin
AU  - Rehan Ahmad
AU  - Michio Kosugi
AU  - Turner Kufe
AU  - Baldev Vasir
AU  - David Avigan
AU  - Surender Kharbanda
AU  - Donald Kufe
TI  - Survival of Human Multiple Myeloma Cells Is Dependent on MUC1 C-Terminal Transmembrane Subunit Oncoprotein Function
AID  - 10.1124/mol.110.065011
DP  - 2010 Aug 01
TA  - Molecular Pharmacology
PG  - 166--174
VI  - 78
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/78/2/166.short
4100  - http://molpharm.aspetjournals.org/content/78/2/166.full
SO  - Mol Pharmacol2010 Aug 01; 78
AB  - The MUC1 C-terminal transmembrane subunit (MUC1-C) oncoprotein is a direct activator of the canonical nuclear factor-κB (NF-κB) RelA/p65 pathway and is aberrantly expressed in human multiple myeloma cells. However, it is not known whether multiple myeloma cells are sensitive to the 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 the interaction between MUC1-C and NF-κB p65 and 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.