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

Osteopontin (OPN) is a secreted, integrin-binding protein which has been implicated in cancer, as well as other pathologies and some aspects of normal development. Here we focus on the role of OPN in breast cancer. We describe studies that have shown that OPN plays a role in normal mammary gland development as well as in progression of breast cancer. We also summarize studies that have shown that OPN can play a functional role in malignancy of breast cancer. At least some of these effects are mediated by specific cell surface integrins (alpha(v)beta3 vs. alpha(v)beta1 and alpha(v)beta5) and lead to increased cell migration, activation of growth factor/receptor pathways (e.g. HGF and EGF), and increased proteolytic enzyme activity (e.g. uPA). We also summarize clinical studies that show that OPN levels in tumors and blood are elevated in women with metastatic breast cancer and may offer promise as prognostic markers in breast cancer.
 ...
PMID:The role of osteopontin in breast cancer: clinical and experimental studies. 1201 31

Recent studies reported an increased expression of osteopontin (OPN) in metastatic breast cancer cells, but the mechanisms modulating OPN production and the interaction of the cells with the secreted protein are far from clear. In this work, we utilized as an experimental system the cell line MDA-231 and we showed that HGF and M-CSF significantly enhance their adhesion onto OPN. Furthermore, in the presence of HGF and M-CSF, MDA-231 cells can adhere when plated onto BSA via increased OPN secretion. Moreover HGF and M-CSF induce de novo synthesis of OPN. In conclusion, these data suggest that HGF and M-CSF stimulate OPN production by MDA-231 cells, and that OPN is subsequently used as a substrate for cell adhesion.
 ...
PMID:HGF and M-CSF modulate adhesion of MDA-231 breast cancer cell by increasing osteopontin secretion. 1245 16

The protooncogene c-met encodes the tyrosine kinase receptor for the hepatocyte growth factor/scatter factor (HGF/SF). While overexpression of c-met is documented in many types of tumors, the mechanism of c-met regulation remains elusive. Here, we demonstrate Daxx as a repressor of c-met transcription. The expression of c-met is elevated in Daxx knockout mouse cells and is reversed by Daxx reconstitution. C-met promoter analysis of Daxx-/- cells reveled changes in chromatin acetylation, but not in DNA methylation. Daxx binds to the mouse c-met promoter and Daxx-binding region is sufficient for transcription repression, while HDAC2 is associated with c-met promoter mostly in Daxx+/+ cells, pointing to Daxx-dependent HDAC2 recruitment as a potential mechanism of c-met repression. HGF-induced cell mobility and invasion confirmed augmented activity of c-Met/HGF pathway in Daxx-/- cells. Finally, inverse correlation between Daxx and c-Met in cancer cell lines and in metastatic breast cancer specimens suggests potential function of Daxx as a c-met repressor during cancer progression.
 ...
PMID:Regulation of c-met expression by transcription repressor Daxx. 1795 15

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials.
...
PMID:Functional consequence of the MET-T1010I polymorphism in breast cancer. 2560 52