Author/Authors :
Lang، نويسنده , , Jing-Yu and Hsu، نويسنده , , Jennifer L. and Meric-Bernstam، نويسنده , , Funda and Chang، نويسنده , , Chun-Ju and Wang، نويسنده , , Qingfei and Bao، نويسنده , , Yi and Yamaguchi، نويسنده , , Hirohito and Xie، نويسنده , , Xiaoming and Woodward، نويسنده , , Wendy A. and Yu، نويسنده , , Dihua and Hortobagyi، نويسنده , , Gabriel N. and Hung، نويسنده , , Mien-Chie، نويسنده ,
Abstract :
Summary
cancer initiating cells (BCICs), which can fully recapitulate the tumor origin and are often resistant to chemo- and radiotherapy, are currently considered as a major obstacle for breast cancer treatment. Here, we show that BIKDD, a constitutively active mutant form of proapoptotic gene, BIK, effectively induces apoptosis of breast cancer cells and synergizes with lapatinib. Most importantly, BikDD significantly reduces BCICs through co-antagonism of its binding partners Bcl-2, Bcl-xL, and Mcl-1, suggesting a potential therapeutic strategy targeting BCICs. Furthermore, we developed a cancer-specific targeting approach for breast cancer that selectively expresses BikDD in breast cancer cells including BCICs, and demonstrated its potent antitumor activity and synergism with lapatinib in vitro and in vivo.
