原创力文档selective small molecule stat3 inhibitor reduces breast cancer tumor-initiating cells and improves recurrence free survival in a human-xenograft model选择性小分子stat3抑制剂减少乳腺癌复发肿瘤起源细胞,提高自由生存human-xenograft模型.pdfVIP
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selective small molecule stat3 inhibitor reduces breast cancer tumor-initiating cells and improves recurrence free survival in a human-xenograft model选择性小分子stat3抑制剂减少乳腺癌复发肿瘤起源细胞,提高自由生存human-xenograft模型
Selective Small Molecule Stat3 Inhibitor Reduces Breast
Cancer Tumor-Initiating Cells and Improves Recurrence
Free Survival in a Human-Xenograft Model
1 1 1 4 4
Bhuvanesh Dave , Melissa D. Landis , Lacey E. Dobrolecki , Meng-Fen Wu , Xiaomei Zhang ,
3 4 3 4 2
Thomas F. Westbrook , Susan G. Hilsenbeck , Dan Liu , Michael T. Lewis , David J. Tweardy ,
Jenny C. Chang1*
1The Methodist Cancer Center, Houston, Texas, United States of America, 2 Department of Infectious Diseases, Departments of Molecular Cellular Biology and
Radiology, Baylor College of Medicine, Houston, Texas, United States of America, 3 Department of Biochemistry and Molecular Biology, Departments of Molecular
Cellular Biology and Radiology, Baylor College of Medicine, Houston, Texas, United States of America, 4 Lester and Sue Smith Breast Center, Departments of Molecular
Cellular Biology and Radiology, Baylor College of Medicine, Houston, Texas, United States of America
Abstract
Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined
a CD44+/CD24 2/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as
a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines
SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the
percentage of cells expressing TIC markers (CD44+/CD24 2/low and ALDH+) and mammosphere formation in p-Stat3
overexpressing human breast cancer xenog
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