FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27

• Published in: Biochemical and biophysical research communications Vol. 456; no. 1; pp. 232 - 237
• Main Authors: Zhao, Yi-Fan, Zhao, Jing-Yu, Yue, Hong, Hu, Ke-Shi, Shen, Hao, Guo, Zheng-Gang, Su, Xiao-Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.01.2015
• Subjects: 60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; Antineoplastic Agents - pharmacology; Breast cancer; Breast Neoplasms - metabolism; CARCINOGENESIS; CELL CYCLE; Cell Line, Tumor; CELL PROLIFERATION; Cell Separation; Cell Survival; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Disease Progression; Drug resistance; Drug Resistance, Neoplasm; DRUGS; Female; Flow Cytometry; Forkhead Transcription Factors - metabolism; FOXD1; Gene Expression Regulation, Neoplastic; Humans; KIDNEYS; MAMMARY GLANDS; NEOPLASMS; ONCOGENES; ONTOGENESIS; p27; PATIENTS; PHASE TRANSFORMATIONS; RNA, Small Interfering - metabolism; THERAPY; TRANSCRIPTION FACTORS; Transcription, Genetic; Up-Regulation; Breast cancer; FOXD1; p27; Drug resistance; Cell cycle
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.11.064

•FOXD1 is up-regulated in breast cancer tissues.•FOXD1 promotes breast cancer cell proliferation and chemoresistance by inducing G1 to S transition.•FOXD1 transcriptionally suppresses p27 expression. Forkhead transcription factors are essential for diverse processes in early embryonic development and organogenesis. As a member of the forkhead family, FOXD1 is required during kidney development and its inactivation results in failure of nephron progenitor cells. However, the role of FOXD1 in carcinogenesis and progression is still limited. Here, we reported that FOXD1 is a potential oncogene in breast cancer. We found that FOXD1 is up-regulated in breast cancer tissues. Depletion of FOXD1 expression decreases the ability of cell proliferation and chemoresistance in MDA-MB-231 cells, whereas overexpression of FOXD1 increases the ability of cell proliferation and chemoresistance in MCF-7 cells. Furthermore, we observed that FOXD1 induces G1 to S phase transition by targeting p27 expression. Our results suggest that FOXD1 may be a potential therapy target for patients with breast cancer.