Smoothened activates breast cancer stem-like cell and promotes tumorigenesis and metastasis of breast cancer

摘要

Smoothened (Smo) is a G protein-coupled receptor protein encoded by the Smo gene of the hedgehog signalling pathway, which is thought to play an important role in maintaining organ patterning, cell differentiation and self-renewal. The possible role of Smo in the process of tumorigenesis and metastasis of breast cancer still remains unclear. The present experiments were to investigate the effect of Smo on activating breast cancer stem-like CD44(+) CD24 cells and the tumorigenesis and metastasis of breast cancer. By injected CD44(+) CD24 cells (1 x 10(4)) into the cleared fat pad of NOD/SCID mice, it was observed that CD44(+) CD24 cells possess higher tumor-initiating capacity and metastasis properties than equal numbers of non-CD44(+) CD24 cells. The mRNA and protein expressions of Smo in CD44(+) CD24 cells were higher than those in non-CD44+ CD24 cells, indicating that Smo may play a role in maintaining breast cancer stem cell features. qRT-PCR results revealed that expressions of STAT3, Bcl-2 and cyclinD1 mRNA in MCF-7 cells were decreased after transfected by Smo siRNA. In addition, the expressions of MMP-2 and MMP-9 were downregulated in MCF-7 cells after Smo expression was inhibited. Smo inhibition may be a possible therapeutic target that potentially suppresses breast tumor formation and development. (C) 2014 Elsevier Masson SAS. All rights reserved.