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Catenin Signalling (catenin + signalling)
Selected AbstractsBMP-9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/,-catenin signallingJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Ni Tang Abstract Bone morphogenetic protein 9 (BMP-9) is a member of the transforming growth factor (TGF)-,/BMP superfamily, and we have demonstrated that it is one of the most potent BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). Here, we sought to investigate if canonical Wnt/,-catenin signalling plays an important role in BMP-9-induced osteogenic differentiation of MSCs. Wnt3A and BMP-9 enhanced each other's ability to induce alkaline phosphatase (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was shown to inhibit BMP-9-induced ALP activity more effectively than Dkk1, whereas a secreted form of LPR-5 or low-density lipoprotein receptor-related protein (LRP)-6 exerted no inhibitory effect on BMP-9-induced ALP activity. ,-Catenin knockdown in MSCs and MEFs diminished BMP-9-induced ALP activity, and led to a decrease in BMP-9-induced osteocalcin reporter activity and BMP-9-induced expression of late osteogenic markers. Furthermore, ,-catenin knockdown or FrzB overexpression inhibited BMP-9-induced mineralization in vitro and ectopic bone formation in vivo, resulting in immature osteogenesis and the formation of chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that BMP-9 induced recruitment of both Runx2 and ,-catenin to the osteocalcin promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly through interactions between ,-catenin and Runx2, plays an important role in BMP-9-induced osteogenic differentiation of MSCs. [source] Systematic review: molecular chemoprevention of colorectal malignancy by mesalazineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. LYAKHOVICH Summary Background, Mesalazine (mesalamine) (5-ASA) is considered an anti-inflammatory drug for the treatment of inflammatory bowel disease. It is well tolerated by most patients and induces mucosal healing specifically in ulcerative colitis. Besides its anti-inflammatory properties, 5-ASA has been studied for cancer inhibitory activities as it seems to reduce colorectal cancer incidence in patients using this drug for long periods of time. However, detailed molecular mechanisms of drug action are vague. Aims, To evaluate known molecular mechanisms of 5-ASA on chemoprevention of colorectal malignancy. Methods, Systematic review with search terms ,5 aminosalicylic acid, mesalazine, 5-ASA, mesalazine, molecular mechanisms, chemoprevention' between 2006 and August 2009. Results, A total of 48 studies were retrieved that link 5-ASA chemopreventive properties to five distinct pathways. These include interference with cell cycle progression (12 references), scavenging of reactive oxygen- or nitrogen-derived metabolites (16 references), TNF-,/TGF-ß signalling (11 references), WNT/,-catenin signalling (5 references) and anti-bacterial properties (4 references). Conclusions, In the recent years, a large amount of molecular data has accumulated supporting the notion that 5-ASA biological effects interfere with colorectal cancer development. These molecular pathways are of special interest in the search for 5-ASA's molecular target(s) and development of novel chemopreventive compounds. Aliment Pharmacol Ther,31, 202,209 [source] Mesalazine inhibits the , -catenin signalling pathway acting through the upregulation of ,-protocadherin gene in colo-rectal cancer cellsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010S. PARENTI Summary Background, Several reports indicate that mesalazine (5-aminosalicylic acid, 5-ASA) is a promising candidate for the chemoprevention of colo-rectal cancer because of its ability to reach the purpose avoiding the unwanted side effects usually associated with prolonged administration of nonsteroidal anti-inflammatory drugs. This activity of 5-ASA is probably the consequence of a number of effects determined on colo-rectal cancer cells, consisting of reduced proliferation, increased apoptosis and activation of cell cycle checkpoints and DNA repair processes. A recent observation has suggested that inhibition of ,-catenin signalling could induce these cellular effects. Aim, To characterize better the capacity of 5-ASA to inhibit the ,-catenin signalling pathway. Methods, Genes belonging to the ,-catenin signalling pathway were analysed in colo-rectal cancer cell lines treated with 5-ASA using a combination of laboratory assays that are able to detect their phenotypic expression and functional activity. Results, The results obtained indicated that 5-ASA induces the expression of a protein called ,-protocadherin that belongs to the cadherin superfamily and is able to sequester ,-catenin on the plasmatic membrane of treated cells hampering its function. Conclusion, These findings suggest that ,-protocadherin might be employed as a biological marker to monitor the chemopreventive efficacy of 5-ASA. [source] Controlling the stem cell niche: right time, right place, right strengthBIOESSAYS, Issue 1 2006Catherin Niemann Wnt signalling through ,-catenin plays a pivotal role during embryonic pattern formation, cell fate determination and tissue homeostasis in the adult organism. In the skin, as in many other tissues, Wnt/,-catenin signalling can control lineage determination and differentiation. However, it was not known whether Wnt/,-catenin signalling is an immediate regulator of the stem cell niche in skin tissue. A recent publication now provides evidence that Wnt/,-catenin signalling exerts a direct effect on the stem cell compartment by inducing quiescent stem cells to enter the cell cycle during early stages of hair follicle regeneration. In addition, the authors demonstrate that ,-catenin is required for maintenance of the stem cell pool in the tissue.1 The data suggest that a gradient in Wnt/,-catenin activity levels can induce different responses within distinct cell populations reflected by activation of distinct transcriptional profiles. BioEssays 28:1,5, 2006. © 2005 Wiley Periodicals, Inc. [source] | ||||||||||