Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility
Journal
Journal of Clinical Investigation
Journal Volume
123
Journal Issue
3
Pages
1082-1095
Date Issued
2013
Author(s)
Kuo T.-C.
Chang Y.-W.
Hong C.-C.
Lee W.-J.
Chen M.-W.
Chiou J.
Yu P.
Chen P.-S.
Wang M.-Y.
Hsiao M.
Su J.-L.
Kuo M.-L.
Abstract
Angiopoietin-like protein 1 (ANGPTL1) is a potent regulator of angiogenesis. Growing evidence suggests that ANGPTL family proteins not only target endothelial cells but also affect tumor cell behavior. In a screen of 102 patients with lung cancer, we found that ANGPTL1 expression was inversely correlated with invasion, lymph node metastasis, and poor clinical outcomes. ANGPTL1 suppressed the migratory, invasive, and metastatic capabilities of lung and breast cancer cell lines in vitro and reduced metastasis in mice injected with cancer cell lines overexpressing ANGPTL1. Ectopic expression of ANGPTL1 suppressed the epithelial-to-mesenchymal transition (EMT) by reducing the expression of the zinc-finger protein SLUG. A microRNA screen revealed that ANGPTL1 suppressed SLUG by inducing expression of miR-630 in an integrin α1β1/FAK/ERK/SP1 pathway-dependent manner. These results demonstrate that ANGPTL1 represses lung cancer cell motility by abrogating the expression of the EMT mediator SLUG.
SDGs
Other Subjects
angiopoietin 1; CCAAT enhancer binding protein alpha; fibronectin; microRNA; microRNA 630; nerve cell adhesion molecule; transcription factor Slug; transcription factor Sp1; unclassified drug; uvomorulin; very late activation antigen 1; vimentin; animal cell; animal experiment; animal model; animal tissue; article; cancer cell culture; cancer inhibition; cancer invasion; cancer prognosis; cell invasion; cell migration; cell motility; controlled study; disease free survival; down regulation; female; gene overexpression; human; human cell; human tissue; in vitro study; lung adenocarcinoma; lung alveolus cell carcinoma; lymph node metastasis; male; mouse; nonhuman; nucleotide sequence; outcome assessment; overall survival; priority journal; protein expression; regulatory mechanism; signal transduction
Type
journal article