Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As malignant breast cancers progress, they acquire the ability to spread to other regions of the body, including bone and lung, but the molecular mechanism underlying the increase in metastatic potential is not fully understood. Here we studied murine 4T1E/M3 highly bone marrow metastatic breast cancer cells, which we established previously. These cells show upregulated expression of bone morphogenetic protein (BMP) 7 and BMP receptors, as well as augmented phosphorylation of Smad1/5/8. Both anchorage-independent cell growth measured in colony forming assays and cell migration measured in wound healing assays were suppressed in 4T1E/M3 cells following treatment with a neutralizing anti-BMP7 antibody or knockdown of BMP7 gene expression. In addition, metastasis of 4T1E/M3 cells to the spine and lung and intracellular levels of phosphorylated Smad1/5/8 were suppressed by knocking down BMP7. Conversely, overexpression of BMP7 in the weakly metastatic parental 4T1E cells augmented their anchorage-independent growth, migration and metastasis to spine and lung. Taken together, our results strongly suggest that augmented autocrine BMP7 signaling leads to increases in the anchorage-independent cell growth, migration and metastatic potential in our bone marrow metastatic breast cancer model.
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PMID:Augmented autocrine bone morphogenic protein (BMP) 7 signaling increases the metastatic potential of mouse breast cancer cells. 2227 90

A recent Cell publication demonstrates that the secreted antagonist of transforming growth factor-beta ligands, Coco, can re-activate previously dormant metastatic breast cancer cells specifically in the lung by inhibiting bone morphogenetic protein (BMP) signaling. The authors provided evidence for a connection between Coco/BMP signaling and molecular and cellular traits of cancer stem cells. Their findings represent a significant advance in our understanding of metastatic dormancy, an extremely important clinical issue that remains understudied. Equally as important, this study also opens interesting avenues for future research.
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PMID:BMP/Coco antagonism as a deterministic factor of metastasis dormancy in lung. 2332 Jun 13