P1-04-01: The Mechanism of Anti-Breast Cancer TICs Effect of Pyrvinium Pamoate Is through WNT/beta-Catenin Signaling.

Abstract

We have previously shown that pyrvinium pamoate can decrease breast cancer TICs in vitro and shrink the tumor size in vivo. Although pyrvinium pamoate has been shown to target beta-catenin through activating CK-1alpha in a vitro model, the mechanism of its anti-breast cancer TICs effect is unknown. Herein, we use a constitutively active WNT/beta-catenin signaling construct EBETAP (ref) to determine if the anti-breast TIC effect of pyrvinium pamoate is through WNT/beta-catenin signaling. Using aldefluor expression and mammosphere formation efficiency as TIC surrogate assays, we found that TICs of SUM-159 transfected with EBETAP construct are resistant to pyrvinium pamoate treatment compared to control cells. Moreover, microarray analysis reveals a series of genes and signaling downstream of WNT-catenin were down-regulated in SUM-159 cells treated with pyrvinium pamoate. In summary, mechanism of anti-breast cancer TICs effect of pyrvinium pamoate is through WNT/beta-catenin signaling. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-04-01.