Talk title | Targeting KLF5 in Triple Negative Breast Cancer |
Speaker | Prof. Ceshi CHEN Professor Kunming Institute of Zoology, Chinese Academy of Sciences, China |
Date & Time | 15 December 2017 (Friday) 10:00-11:00 |
Venue | Room G003, E12 Building (University of Macau) |
Abstract | Out of the breast cancer subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis without effective targeted therapies. A stem cell transcription factor KLF5 is over-expressed in basal type TNBC and promotes cell proliferation, survival and stemness. Using a breast specific knockout mouse model, we showed that Klf5 promotes breast development and breast cancer initiation. We demonstrated that KLF5 functions through several direct target genes, including FGF-BP1, mPGES1, TNFAIP2 and Slug. The KLF5 protein stability was regulated by the ubiquitin-proteasome pathway. Transcriptionally, KLF5 is induced by progesterone receptor upon progesterone stimulation. Mifepristone suppresses basal TNBC stem cells by down-regulating KLF5 expression through inducing the expression of miR-153. Metformin, a first-line drug for type 2 diabetes mellitus, decreased the percentage of TNBC stem cells partially through the downregulation of the expression of KLF5, in TNBC cell lines. These findings suggest that KLF5 is a promising therapeutic target in TNBC and several old drugs may be used for TNBC treatment in the future. |