TY - JOUR
T1 - BikDD eliminates breast cancer initiating cells and synergizes with lapatinib for breast cancer treatment
AU - Lang, Jing Yu
AU - Hsu, Jennifer L.
AU - Meric-Bernstam, Funda
AU - Chang, Chun Ju
AU - Wang, Qingfei
AU - Bao, Yi
AU - Yamaguchi, Hirohito
AU - Xie, Xiaoming
AU - Woodward, Wendy A.
AU - Yu, Dihua
AU - Hortobagyi, Gabriel N.
AU - Hung, Mien Chie
N1 - Funding Information:
We thank Bill Spohn and Dr. Zhenbo Han for providing the HLDC liposome. We also thank Dr. Stephanie A. Miller for editing this article. This work was supported by NIH grants Breast SPORE (CA116199) and P01 (CA99031), MDACC/CMUH Sister Institution Fund, Breast Cancer Research Foundation, National Breast Cancer Foundation, Inc., Patel Memorial Breast Cancer Research Fund, The Center for Biological Pathways and Cancer Center Support Grant (CA16672) of The University of Texas MD Anderson Cancer Center, NSC-3111-B-039, NSC-2632-B-039-001, and Cancer Center Research of Excellence Grant (DOH-TD-C-111-005). The authors have declared that no conflict of interest exists. In memoriam, Mrs. Serena Lin-Guo for her courageous fight against breast cancer.
PY - 2011/9
Y1 - 2011/9
N2 - Breast 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.
AB - Breast 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.
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U2 - 10.1016/j.ccr.2011.07.017
DO - 10.1016/j.ccr.2011.07.017
M3 - Article
C2 - 21907925
AN - SCOPUS:80052594392
SN - 1535-6108
VL - 20
SP - 341
EP - 356
JO - Cancer cell
JF - Cancer cell
IS - 3
ER -