Prof. Ju Wang
Jinan University, China
Title: BMP-2 induces EMT and breast cancer stemness through Rb and CD44
Abstract:
Bone morphogenetic protein
2 (BMP-2) has been reported
to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer
xenograft models. To investigate the role of BMP-2 in the development of breast cancer
stem cells (BCSCs), and to
further elucidate the mechanisms underlying its influence on breast cancer
metastasis, we conducted a comprehensive molecular study
using breast cancer
cell lines and clinical samples.
Our results showed
that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT
signal pathway. In addition, the Smad signaling pathways are implicated in upregulation of CD44 protein
expression by BMP-2.
It was suggested that cross-talk exists
between Rb and
CD44 signaling pathways, as recombinant human
BMP-2 (rhBMP-2) was found to regulate
CD44 expression partly
through Rb signals. In clinical tissues, BMP-2 was positively and negatively correlated with CD44 and Rb
expression, respectively. Based
on the in vitro and in
vivo results, we have
established an integrated mechanism by which
rhBMP-2 induces EMT and stemness of breast cancer
cells via the Rb and CD44 signaling pathways, which then contribute to breast cancer metastasis. These findings may be helpful
for developing new strategies for the treatment and prognosis of advanced breast cancer.
Biography:
Wang Ju，Doctor, Professor, Doctoral supervisor in Jinan University，CSO in Guangzhou Sanrosee biotech Ltd.
Worked one year in Hongkong Biological Engineering Research Institute, 1996-1997;
Drug development 6 years in Guangdong Tian Pu Biochemical Pharmaceutical Co., Ltd, 1994-2001;
College of life science and technology, Jinan University(also in National Engineering Research Centre of Genetic Medicine), 2001-up to now.
Funds:
Presided 16 scientific research pojects, such as:
1. the“significant New Drug Creation” project of the Ministry of Science and Technology of China
2. the“significant New Drug Creation” project of Guangdong province
3. the National Natural Science Foundation program of China
4. the “China-UK bridge” project (Guangzhou Economic & Technological Development Zone)
5. Guangdong province production project
6. Science and Technology project of Guangdong province
Publications
A total of 23 SCI papers on the academic journals such as Angewandte Chemie, Mol Cancer Ther, Molecular Medicine, etc.
Patents
2PCT(submitted, 1 authorized), 13 China invention patent submitted( 8 authorized)