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24918049
Staphylococcal nuclease domain containing-1 (SND1) promotes migration and invasion via angiotensin II type 1 receptor (AT1R) and TGFβ signaling.

FEBS Open Bio, 2014;4:353-61.

Santhekadur PK[1], Akiel M[1], Emdad L[1], Gredler R[1], Srivastava J[1], Rajasekaran D[1], Robertson CL[1], Mukhopadhyay ND[2], Fisher PB[3], Sarkar D[3]

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PMID: 24918049DOI: 10.1016/j.fob.2014.03.012

Impact factor: 2.792

Abstract
Staphylococcal nuclease domain containing-1 (SND1) is overexpressed in human hepatocellular carcinoma (HCC) patients and promotes tumorigenesis by human HCC cells. We now document that SND1 increases angiotensin II type 1 receptor (AT1R) levels by increasing AT1R mRNA stability. This results in activation of ERK, Smad2 and subsequently the TGFβ signaling pathway, promoting epithelial-mesenchymal transition (EMT) and migration and invasion by human HCC cells. A positive correlation was observed between SND1 and AT1R expression levels in human HCC patients. Small molecule inhibitors of SND1, alone or in combination with AT1R blockers, might be an effective therapeutic strategy for late-stage aggressive HCC.

Keywords: ACE, angiotensin-I converting enzyme; ACE-I, ACE inhibitors; AT1R; AT1R, angiotensin II type 1 receptor; EMT, epithelial–mesenchymal transition; FDR, false discovery rate; HCC, human hepatocellular carcinoma; Invasion; LP, losartan potassium; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NASH, non-alcoholic steatohepatitis; PAI-1; PAI-1, plasminogen activator inhibitor-1; RISC, RNA-induced silencing complex; SND1; SND1, Staphylococcal nuclease domain containing-1; TGFβ

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