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000127177 0247_ $$2doi$$a10.1158/0008-5472.CAN-15-0997
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000127177 0247_ $$2ISSN$$a0099-7013
000127177 0247_ $$2ISSN$$a0099-7374
000127177 0247_ $$2ISSN$$a1538-7445
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000127177 1001_ $$0P:(DE-He78)60800c1f5fff167ebb246fc76416cee6$$aMudduluru, Giridhar$$b0$$eFirst author$$udkfz
000127177 245__ $$aA Systematic Approach to Defining the microRNA Landscape in Metastasis.
000127177 260__ $$aPhiladelphia, Pa.$$bAACR$$c2015
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000127177 520__ $$aThe microRNA (miRNA) landscape changes during the progression of cancer. We defined a metastasis-associated miRNA landscape using a systematic approach. We profiled and validated miRNA and mRNA expression in a unique series of human colorectal metastasis tissues together with their matched primary tumors and corresponding normal tissues. We identified an exclusive miRNA signature that is differentially expressed in metastases. Three of these miRNAs were identified as key drivers of an EMT-regulating network acting though a number of novel targets. These targets include SIAH1, SETD2, ZEB2, and especially FOXN3, which we demonstrated for the first time as a direct transcriptional suppressor of N-cadherin. The modulation of N-cadherin expression had significant impact on migration, invasion, and metastasis in two different in vivo models. The significant deregulation of the miRNAs defining the network was confirmed in an independent patient set as well as in a database of diverse malignancies derived from more than 6,000 patients. Our data define a novel metastasis-orchestrating network based on systematic hypothesis generation from metastasis tissues.
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000127177 650_7 $$2NLM Chemicals$$aAntigens, CD
000127177 650_7 $$2NLM Chemicals$$aCDH2 protein, human
000127177 650_7 $$2NLM Chemicals$$aCadherins
000127177 650_7 $$2NLM Chemicals$$aCell Cycle Proteins
000127177 650_7 $$2NLM Chemicals$$aFOXN3 protein, human
000127177 650_7 $$2NLM Chemicals$$aHomeodomain Proteins
000127177 650_7 $$2NLM Chemicals$$aMIRN135 microRNA, human
000127177 650_7 $$2NLM Chemicals$$aMIRN210 microRNA, human
000127177 650_7 $$2NLM Chemicals$$aMIRN218 microRNA, human
000127177 650_7 $$2NLM Chemicals$$aMicroRNAs
000127177 650_7 $$2NLM Chemicals$$aNuclear Proteins
000127177 650_7 $$2NLM Chemicals$$aRepressor Proteins
000127177 650_7 $$2NLM Chemicals$$aZEB2 protein, human
000127177 650_7 $$0EC 2.1.1.43$$2NLM Chemicals$$aHistone-Lysine N-Methyltransferase
000127177 650_7 $$0EC 2.1.1.43$$2NLM Chemicals$$aSet2 protein, human
000127177 650_7 $$0EC 2.3.2.27$$2NLM Chemicals$$aUbiquitin-Protein Ligases
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000127177 7001_ $$0P:(DE-He78)54a8723466e5d487247f3d93d51c66bc$$aAbba, Mohammed Lawan$$b1$$udkfz
000127177 7001_ $$0P:(DE-HGF)0$$aBatliner, Jasmin$$b2
000127177 7001_ $$0P:(DE-He78)e22573706cfe9748cc0e45a526c2bfef$$aPatil, Nitin Shaligram$$b3$$udkfz
000127177 7001_ $$0P:(DE-HGF)0$$aScharp, Maike$$b4
000127177 7001_ $$0P:(DE-HGF)0$$aLunavat, Taral R$$b5
000127177 7001_ $$0P:(DE-HGF)0$$aLeupold, Jörg Hendrik$$b6
000127177 7001_ $$0P:(DE-HGF)0$$aOleksiuk, Olga$$b7
000127177 7001_ $$0P:(DE-He78)5482b9f7e4c4ff6a3a4d7c860a1bce61$$aJuraeva, Dilafruz$$b8$$udkfz
000127177 7001_ $$aThiele, Wilko$$b9
000127177 7001_ $$aRothley, Melanie$$b10
000127177 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b11$$udkfz
000127177 7001_ $$aBen-Neriah, Yinon$$b12
000127177 7001_ $$aSleeman, Jonathan$$b13
000127177 7001_ $$0P:(DE-He78)69067807288b48415ceb4abc43b9ad54$$aAllgayer, Heike$$b14$$eLast author$$udkfz
000127177 773__ $$0PERI:(DE-600)2036785-5$$a10.1158/0008-5472.CAN-15-0997$$gVol. 75, no. 15, p. 3010 - 3019$$n15$$p3010 - 3019$$tCancer research$$v75$$x1538-7445$$y2015
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