Targeting BMP9-Promoted Human Osteosarcoma Growth by Inactivation of Notch Signaling.

Targeting BMP9-Promoted Human Osteosarcoma Growth by Inactivation of Notch Signaling.
Curr Cancer Drug Targets. 2014 Mar 4;
Authors: Li R, Zhang W, Cui J, Shui W, Yin L, Wang Y, Zhang H, Wang N, Wu N, Nan G, Chen X, Wen S, Deng F, Zhang H, Zhou G, Liao Z, Zhang J, Zhang Q, Yan Z, Liu W, Zhang Z, Ye J, Deng Y, Luu HH, Haydon RC, He TC, Deng ZL
Abstract
Osteosarcoma (OS) is the most common primary malignancy of bone and usually associated with poor prognosis due to its high incidence of metastasis and chemoresistance. Molecular pathogenesis of OS is poorly understood. We previously showed that OS cells are refractory to BMP9-induced osteogenesis and respond favorably for proliferation and tumor growth. Here we investigate if Notch signaling mediates the BMP9-promoted cell proliferation and tumor growth of human osteosarcoma (OS). We find that the expression of Notch1, Notch2, Notch3, DLL1, JAG1 and JAG2 is readily detected in most of the tested OS cell lines. BMP9-promoted OS cell proliferation, migration, cell cycle S/G2 progression are effectively inhibited by a dominant-negative mutant of Notch1 (dnNotch1) or the -secretase inhibitor Compound E (ComE). Furthermore, BMP9-promoted tumor growth and osteolytic lesions in vivo are significantly inhibited by dnNotch1. BMP9 up-regulates the expression of Notch1, Notch3, DLL1, and JAG1 in OS cells. Accordingly, BMP9 stimulation induces a nuclear accumulation of NICD, which is blocked by ComE. Our ...

Source: Current Cancer Drug Targets - March 4, 2014 Category: Cancer & Oncology Authors: Li R, Zhang W, Cui J, Shui W, Yin L, Wang Y, Zhang H, Wang N, Wu N, Nan G, Chen X, Wen S, Deng F, Zhang H, Zhou G, Liao Z, Zhang J, Zhang Q, Yan Z, Liu W, Zhang Z, Ye J, Deng Y, Luu HH, Haydon RC, He TC, Deng ZL Tags: Curr Cancer Drug Targets Source Type: research