Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ovarian cancer is a highly invasive and metastatic disease with a poor prognosis if diagnosed at an advanced stage, which is often the case. Recent studies argue that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the relevant molecular mechanisms in this setting are not well-understood. Here, we report findings from an siRNA screen that identified the homeobox transcription factor ALX1 as a novel regulator of EMT. RNA interference-mediated attenuation of ALX1 expression restored E-cadherin expression and cell-cell junction formation in ovarian cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. Conversely, enforced expression of ALX1 in ovarian cancer cells or nontumorigenic epithelial cells induced EMT. We found that ALX1 upregulated expression of the key EMT regulator Snail (SNAI1) and that it mediated EMT activation and cell invasion by ALX1. Our results define the ALX1/Snail axis as a novel EMT pathway that mediates cancer invasion.
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PMID:ALX1 induces snail expression to promote epithelial-to-mesenchymal transition and invasion of ovarian cancer cells. 2328 9

Osteosarcoma is the most common primary malignant tumor in children and young adults, and the molecular regulation of the invasion of osteosarcoma (OS) remains unknown. In this study, we found that increased expression of ALX1 was associated with the progression of osteosarcoma and that ALX1 protein levels were significantly elevated in matched distant metastases. High ALX1 levels also predict shorter overall survival of osteosarcoma patients. We investigated the therapeutic potential of targeting ALX1 expression using the technique of RNA silencing via short hairpin RNA (shRNA). Synthetic shRNA duplexes against ALX1 were introduced to downregulate the expression of ALX1 in a highly malignant osteosarcoma cell line, U2OS. The results obtained indicated that shRNA targeting of ALX1 could lead to an efficient and specific inhibition of endogenous ALX1 activity. Furthermore, we found that depletion of ALX1 caused a dramatic cell cycle arrest, followed by massive apoptotic cell death, and eventually resulted in a significant decrease in migration and invasion of the osteosarcoma cell line studied.
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PMID:Depletion of ALX1 causes inhibition of migration and induction of apoptosis in human osteosarcoma. 2573 24

Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA), a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines. We applied SCA to mRNA/miRNA expression data from various sources, comparing melanoma cell lines and metastases. The signature obtained was associated with phenotypic characteristics in vitro, and the core genes CAPN3 and TRIM63 were implicated in melanoma cell migration/invasion. About 90% of the melanoma signature genes belong to an intrinsic network of transcription factors governing neural development (TFAP2A, DLX2, ALX1, MITF, PAX3, SOX10, LEF1, and GAS7) and miRNAs (211-5p, 221-3p, and 10a-5p). The SCA signature effectively discriminated between two subpopulations of melanoma patients differing in overall survival, and classified MEKi/BRAFi-resistant and -sensitive melanoma cell lines.
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PMID:New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis. 2648 59