Open AccessStaphylococcal nuclease domain containing‐1 (SND1) promotes migration and invasion via angiotensin II type 1 receptor (AT1R) and TGFβ signaling
Author(s) -
Santhekadur Prasanna K.,
Akiel Maaged,
Emdad Luni,
Gredler Rachel,
Srivastava Jyoti,
Rajasekaran Devaraja,
Robertson Chadia L.,
Mukhopadhyay Nitai D.,
Fisher Paul B.,
Sarkar Devanand
Publication year - 2014
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2014.03.012
Subject(s) - cancer research , angiotensin ii , receptor , transforming growth factor , signal transduction , chemistry , mapk/erk pathway , microbiology and biotechnology , medicine , biology , biochemistry
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.