Metastasis is the main cause of death in cancer patients and during its development epithelialmesenchymaltransition (EMT) enables cells to migrate into secondary tissues and create new tumorsthere. In this work, we describe E2F1 and E2F2 transcription factors as EMT inhibitors in colorectalcancer cells. We present SLUG as a key regulator of this transition, which appears overexpressed uponE2F1/2 loss. E2F1/2 mediated SLUG gene expression regulation involves SLUG promoter activitymodulation. Moreover, our results reveal that SMAD6 could play an essential role in SLUG regulation,whose expression is activated in the absence of SMAD6. In fact, downregulation of SMAD6, induced byE2F1/2 silencing, activates SLUG promoter and its expression.
prozesuan, epitelio-mesenkima trantsizioak (EMT) ahalbidetzen du minbizi-zelulak jatorrizko ehunetikaskatzea eta, ehun sekundarioetara migratuz, tumore berriak bertan sortzea. Lan honetan, ondestekominbizian gertatzen den EMTan sakondu dugu. E2F1 eta E2F2 transkribapen faktoreek ondestekominbiziko zeluletan EMTaren inhibizioa eta SLUG genearen errepresioa bultzatzen dutela aurkitu dugu.Errepresio hori, neurri batean, SLUGen promotorearen aktibitateari eraginez gauzatzen dela frogatudugu. Badirudi SLUGen erregulazioa SMAD6ren bitartez gertatzen dela, izan ere, SMAD6ren galerak,E2F1/2ren ausentzian, SLUGen adierazpena eta bere promotorearen aktibitatea emendatzen ditu.
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