- Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.
Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.
Oncotarget (2017-10-21)
Ashujit Tagde, Tahireh Markert, Hasan Rajabi, Masayuki Hiraki, Maroof Alam, Audrey Bouillez, David Avigan, Kenneth Anderson, Donald Kufe
PMID29050200
摘要
The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives