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.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Zhong Liu1, *, Ge Liu1, *, Guang-Lin Zhang1, *, Jun Li1, Yan-Qing He2, Shu-Shu Zhang3, Yi Wang1, Wei-Yi He1, Guo-Hua Cheng4, Xuesong Yang2, Jun Xu3, Ju Wang1 1Institute of Biomedicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China 2Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou 510632, China 3Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China 4College of Pharmacy, Jinan University, Guangzhou 510632, China *These authors contributed equally to this work Correspondence to: Ju Wang, email: wangju1688@163.com Keywords: heterocomplex, FGF-2, soluble FGFR2, tumor inhibition, angiogenesis Received: April 03, 2016 Accepted: August 24, 2016 Published: September 16, 2016

In interstitial fibrosis, alveolar epithelial type II (AE2) cells fail to repair damaged epithelium. However, whether this dysfunction is related to fibroblast growth factor (FGF) signal pathway and how it affects the fibrotic process remains unclear. In our study, the medium of the human foetal lung fibroblast cell line MRC-5 (Med) can induce epithelial-to-mesenchymal transition (EMT) in AE2 cells, we also found that TGF-β in Med can induce FGF-2 and CTGF expression in AE2 cells. TGF-β or CTGF exposure trigger a FGFR2 subtype b to c transition which can be supressed by siRNA-CTGF. All together, since FGFR2IIIc have the highest affinity with FGF-2 in all of the FGFRs, we indicate the activation of FGF2 signal pathway was induced by TGF-β, which is the key component of Med Here, we also find the inhibitory effect of msFGFR2c (S252W mutant of soluble FGFR2IIIc extracellular domain) on EMT of mouse primary AE2 cells in pulmonary fibrotic process. In a bleomycin-induced mouse pulmonary fibrosis model, msFGFR2c alleviate pulmonary fibrosis and suppress the decrease in pro-SPC levels. Thus, msFGFR2c can inhibit EMT-induced fibrosis of AE2 cells via FGF-2 signal and AE2 cells is suggested to play an important role in the lung fibrotic process.