@article{0636bbc2d47e46769f89405e80a6e81a,
title = "Targeting brain-adaptive cancer stem cells prohibits brain metastatic colonization of triple-negative breast cancer",
abstract = "Triple-negative breast cancer (TNBC) exhibits more traits possessed by cancer stem cells (CSC) than other breast cancer subtypes and is more likely to develop brain metastases. TNBC patients usually have shorter survival time after diagnosis of brain metastasis, suggesting an innate ability of TNBC tumor cells in adapting to the brain. In this study, we establish novel animal models to investigate early tumor adaptation in brain metastases by introducing both patient-derived and cell line–derived CSC-enriched brain metastasis tumorsphere cells into mice. We discovered astrocyte-involved tumor activation of protocadherin 7 (PCDH7)-PLCb-Ca2{\th}-CaMKII/S100A4 signaling as a mediator of brain metastatic tumor outgrowth. We further identified and evaluated the efficacy of a known drug, the selective PLC inhibitor edelfosine, in suppressing the PCDH7 signaling pathway to prohibit brain metastases in the animal models. The results of this study reveal a novel signaling pathway for brain metastases in TNBC and indicate a promising strategy of metastatic breast cancer prevention and treatment by targeting organ-adaptive cancer stem cells. Significance: These findings identify a compound to block adaptive signaling between cancer stem cells and brain astrocytes.",
author = "Ding Ren and Xiaoping Zhu and Ren Kong and Zhen Zhao and Jianting Sheng and Jiang Wang and Xiaoyun Xu and Jiyong Liu and Kemi Cui and Zhang, {Xiang H.F.} and Hong Zhao and Wong, {Stephen T.}",
note = "Funding Information: We thank all members of the Wong laboratory at Houston Methodist for discussions and assistance with data analysis; Drs. Neal Copeland and Jeffrey Rosen provided helpful comments for the manuscript; Drs. Rebecca Danforth and James Mancuso for their proofreading skills; and Drs. Patricia Steeg and Joan Massague generously provided MDA-MB-231-Br and CN34-Br cell lines. All microscopic imaging experiments were performed at Houston Methodist Research Institute's Advanced Cellular and Tissue Microscope Core Facility. We acknowledge the computational time funding support from the Texas Advanced Computing Center (TACC; Project ID: TG-MCB110130) at the University of Texas in Austin and BlueBioU (IBM POWER 7 Bioscience Computing Core at Rice University) to access super-computing resources. This research was funded by NIHU54 CA149196, NIHR01 CA121225, and John S. Dunn Research Foundation grants (to S.T. Wong), and R01-CA183878 (to X.H.-F. Zhang). Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",
year = "2018",
month = apr,
day = "15",
doi = "10.1158/0008-5472.CAN-17-2994",
language = "English (US)",
volume = "78",
pages = "2052--2064",
journal = "Cancer research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "8",
}