title: BikDD eliminates breast cancer initiating cells and synergizes with lapatinib for breast cancer treatment.
abstract: 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.
authors: Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
authors: Jing-Yu
authors: JY
authors: Lang
authors: Jennifer L
authors: JL
authors: Hsu
authors: Funda
authors: F
authors: Meric-Bernstam
authors: Chun-Ju
authors: CJ
authors: Chang
authors: Qingfei
authors: Q
authors: Wang
authors: Yi
authors: Y
authors: Bao
authors: Hirohito
authors: H
authors: Yamaguchi
authors: Xiaoming
authors: X
authors: Xie
authors: Wendy A
authors: WA
authors: Woodward
authors: Dihua
authors: D
authors: Yu
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: Mien-Chie
authors: MC
authors: Hung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051927:CD24 Antigen / Q000096:biosynthesis; D045744:Cell Line, Tumor; D062506:Claudin-4; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D000077341:Lapatinib; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C096820:BIK protein, human; D051927:CD24 Antigen; C568157:CLDN4 protein, human; D062506:Claudin-4; C568158:Cldn4 protein, mouse; D018960:Hyaluronan Receptors; C579094:Mcl1 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D011799:Quinazolines; D051020:bcl-X Protein; D000077341:Lapatinib; D017239:Paclitaxel