title: Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility.
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 α(1)β(1)/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.
authors: Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: Tsang-Chih
authors: TC
authors: Kuo
authors: Ching-Ting
authors: CT
authors: Tan
authors: Yi-Wen
authors: YW
authors: Chang
authors: Chih-Chen
authors: CC
authors: Hong
authors: Wei-Jiunn
authors: WJ
authors: Lee
authors: Min-Wei
authors: MW
authors: Chen
authors: Yung-Ming
authors: YM
authors: Jeng
authors: Jean
authors: J
authors: Chiou
authors: Pei
authors: P
authors: Yu
authors: Pai-Sheng
authors: PS
authors: Chen
authors: Ming-Yang
authors: MY
authors: Wang
authors: Michael
authors: M
authors: Hsiao
authors: Jen-Liang
authors: JL
authors: Su
authors: Min-Liang
authors: ML
authors: Kuo
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D011379:Prognosis; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C117578:ANGPTL1 protein, human; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D039222:Integrin alpha1beta1; C548399:MIRN630 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors