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.

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Internal Y-shaped bifurcation has been proved to be an advantageous way on improving thermal performance of microchannel heat sinks according to the previous research. Metal foams are known due to their predominate performance such as low-density, large surface area, and high thermal conductivity. In this paper, different parameters of metal foams in Y-shaped bifurcation microchannel heat sinks are designed and investigated numerically. The effects of Reynolds number, porosity of metal foam, and the pore density (PPI) of the metal foam on the microchannel heat sinks are analyzed in detail. It is found that the internal Y-shaped bifurcation microchannel heat sinks with metal foam exhibit better heat transfer enhancement and overall thermal performance. This research provides broad application prospects for heat sinks with metal foam in the thermal management of high power density electronic devices.

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