Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone morphogenetic protein (BMP)-2, a multifunctional member of the transforming growth factor (TGF)-beta superfamily with powerful osteoinductive effects, has various biological activities in a variety of cells. We observed that BMP-2 inhibits cell proliferation in the androgen-dependent human prostate cancer cell line, LNCaP. To investigate the mechanism of inhibition of androgen-dependent growth by BMP-2, we compared the gene expression in LNCaP cells treated with dihydrotestosterone (DHT) to that of LNCaP cells treated with DHT and BMP-2, using DNA microarray analysis. Of 8,400 human genes on the gene chip, 38 genes were up-regulated by >2.0-fold and 48 genes were down-regulated by <0.5-fold by treatment with BMP-2. These genes were involved in a variety of cellular functions, including signal transduction, transcription regulation, enzymes, transporters, structural molecules and translation. RT-PCR analysis showed that CH1CL and BMX were up-regulated and DACH1 and WNT5A were down-regulated by treatment with BMP-2. Furthermore, we detected an increase of WNT5A protein in the medium by DHT and inhibition of the increase by BMP-2. In the present study, we identified several BMP-2-responsive genes in LNCaP cells. Further studies of the roles of these genes may clarify the mechanisms underlying the inhibition of cell proliferation by BMP-2 and identify better approaches for the prevention and treatment of prostate cancer.
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PMID:Alteration of gene expression in response to bone morphogenetic protein-2 in androgen-dependent human prostate cancer LNCaP cells. 1639 28

The ALPL gene is linked to hypophosphatasia, a rare genetic disease. Owing to the inverse relationships between ALPL expression and both the International Federation of Gynecology and Obstetrics (FIGO) stages and histological grades assigned to patients with serous ovarian cancer (SOC), this study was designed to explore the role and possible mechanisms of ALPL in cell motility of high grade SOC (HGSOC). The effects of ALPL overexpression on migration and invasion were detected in HGSOC cell lines SKOV3 and HEY. Gene ontology analysis for differential genes with ALPL overexpression identified several biological processes, including EMT, correlated with cell motility. Genes potentially implicated in EMT and associated with ALPL were screened using The Cancer Genome Atlas (TCGA) database. The WNT receptor Frizzled2 (FZD2) was identified and its role in HGSOC cell motility and survival was investigated. It was found that forced expression of ALPL could inhibit migration, invasion, and EMT in HGSOC cells. It also reduced the expression of FZD2 and its ligand WNT5A, accompanied by suppressed expression of their downstream target phosphorylated-STAT3 (pSTAT3). These effects were initiated via the FZD2 knockdown using siRNA and reversed by recombinant WNT5A protein. The relationship between FZD2 expression and poor HGSOC patient survival was also investigated. This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.
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PMID:ALPL regulates the aggressive potential of high grade serous ovarian cancer cells via a non-canonical WNT pathway. 3097 97