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6月8日清华大学生物论坛 - Yibin Kang
发布时间:2018-06-03关键字:

 

Stromal Niche as Regulator of Stemness, Tumor initiation and Metastasis

 

Yibin Kang, Ph.D.

Warner-Lambert/Parke-Davis Professor of Molecular Biology, Princeton University

 

BiographyProf. Kang received his Ph.D. degree in 2000 from Duke University and his postdoctoral training in Memorial Sloan-Kettering Cancer Center. He joined Princeton Unversity in 2004 and is currently the Warner-Lambert/Parke-Davis Professor of Molecular Biology (Endowed). He pioneered the breast cancer bone metastasis research and expaneded his research interest to normal mammary stem cell development and its role in tumor initiation and metastasis. Prof. Kang received numorous awards in his career. To name a few: he is the reciept of the 2011 Vilcek Prize for Creative Promise in Biomedical Science, 2012 AACR Award for Outstanding Achievement in Cancer Research, 2014 AACR Outstanding Investigator Award for Breast Cancer Research, 2016 Komen Scholar, and 2016 AAAS Fellow.

 

Abstract: The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. Epithelial-niche interactions have been shown to play critical roles in regulating normal and cancer stem cell activity, epithelial-mesenchymal transition (EMT), tumor invasion and metastatic colonization. Macrophages are commonly present in both normal mammary gland and breast cancer, and play critical roles in tumor initiation, progression and metastasis. Dr Kang’s recent studies reveal further dynamic interactions between normal and cancerous mammary stem cells with macrophages. They found that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands, thereby initiating a feedback loop that promotes the function of Dll1+ MaSCs. Dll deletion in the mammary gland also reduce the initiation and progression of Wnt-driven basal like breast cancer, suggesting a conserved role of Dll1 in breast cancer stem cells. Mammary gland cell fate regulators also influence the interaction between stem cells and stromal macrophages. miR-199a promotes stem cell properties in mammary stem cells (MaSCs) and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by macrophages in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER- breast tumors, functionally promotes tumor initiation and metastasis, and is associated with poor clinical outcome. Taken together, these findings support the notion that breast cancer stem cells and normal mammary stem cells share common regulatory mechanisms in their interaction with stromal macrophages, which may be exploited for breast cancer prevention and therapeutics.

 

Time: Jun 8th, 2018, 9:00 am

Venue: Medical Sciences, Room D326

Host: Dr. Hanqiu Zheng

举办单位:清华大学生命科学联合中心

 

 

 




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