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)

MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens and associated with tumor relapse and metastasis. Here, we investigated the expression of MAGEC2 in patients with breast cancer and its clinical effects with underlying mechanisms. The expression levels of MAGEC2 were compared between 420 invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast. Correlations between MAGEC2 expression and clinico-pathologic factors or survival of patients with IDC were analyzed. In addition, MAGEC2 expression levels in tumor tissues dissected from the primary focus and matched tumor-invaded axillary lymph nodes were analyzed in 8 breast cancer patients. The functional effects of MAGEC2 overexpression were assessed in vitro using scratch assay and transwell chamber assay. MAGEC2 expression was increased in metastatic breast cancer in comparison to the non-metastatic. MAGEC2 expression was significantly associated with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive expression have a worse prognosis and a shorter metastasis free interval. Multivariate analyses showed that MAGEC2 expression was an independent risk factor for patient overall survival and metastasis-free survival. Breast cancer cells that overexpressed MAGEC2 had stronger migratory and invasive potential than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were down-regulated in MAGEC2-overexpressing cells compared to controls, whereas mesenchymal markers (vimentin and fibronectin) were upregulated. Our results indicate that MAGEC2 has a role in breast cancer metastasis through inducing epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a novel therapeutic strategy for breast cancer treatment.
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PMID:MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis. 2468 77

Bone metastasis is common in late-stage breast cancer patients and leads to skeletal-related events that affect the quality of life and decrease survival. Numerous miRNAs have been confirmed to be involved in metastatic breast cancer, such as the miR200 family. Our previous study identified microRNA-429 (miR-429) as a regulatory molecule in breast cancer bone metastasis. However, the effects of miR-429 and its regulatory axis in the metastatic breast cancer bone microenvironment have not been thoroughly investigated. We observed a positive correlation between miR-429 expression in clinical tissues and the bone metastasis-free interval and a negative correlation between miR-429 expression and the degree of bone metastasis. We cultured bone metastatic MDA-MB-231 cells and used conditioned medium (CM) to detect the effect of miR-429 on osteoblast and osteoclast cells in vitro. We constructed an orthotopic bone destruction model and a left ventricle implantation model to examine the effect of miR-429 on the metastatic bone environment in vivo. The transfection experiments showed that the expression levels of V-crk sarcoma virus CT10 oncogene homolog-like (CrkL) and MMP-9 were negatively regulated by miR-429. The in vitro coculture experiments showed that miR-429 promoted osteoblast differentiation and that CrkL promoted osteoclast differentiation. The two animal models showed that miR-429 diminished local bone destruction and distant bone metastasis but CrkL enhanced these effects. Furthermore, CrkL and MMP-9 expression decreased simultaneously in response to increased miR-429 expression. These findings further reveal the possible mechanism and effect of the miR-429/CrkL/MMP-9 regulatory axis in the bone microenvironment in breast cancer bone metastasis.
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PMID:MicroRNA-429 inhibits bone metastasis in breast cancer by regulating CrkL and MMP-9. 3170 51