Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility
Tsang-Chih Kuo, … , Jen-Liang Su, Min-Liang Kuo
Tsang-Chih Kuo, … , Jen-Liang Su, Min-Liang Kuo
Published February 22, 2013
Citation Information: J Clin Invest. 2013;123(3):1082-1095. https://doi.org/10.1172/JCI64044.
View: Text | PDF | Corrigendum
Research Article Article has an altmetric score of 12

Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility

  • Text
  • PDF
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.

Authors

Tsang-Chih Kuo, Ching-Ting Tan, Yi-Wen Chang, Chih-Chen Hong, Wei-Jiunn Lee, Min-Wei Chen, Yung-Ming Jeng, Jean Chiou, Pei Yu, Pai-Sheng Chen, Ming-Yang Wang, Michael Hsiao, Jen-Liang Su, Min-Liang Kuo

×

Figure 2

ANGPTL1 inhibits cancer cell motility and metastasis.

Options: View larger image (or click on image) Download as PowerPoint
ANGPTL1 inhibits cancer cell motility and metastasis.
(A) The relative m...
(A) The relative migration and invasion and (B) the ANGPTL1 expression and secreted ANGPTL1 level in a series of cancer cells. (C and D) qRT-PCR analysis of ANGPTL1 and measurement of the migration and invasion in (C) ANGPTL1-overexpressing CL1-5, A549, and MDA-MB-231/I3 cells and (D) ANGPTL1 knockdown CL1-0, MDA-MB-231, H928, and PC14 cells. (E) Measurement of the relative migration in ANGPTL1-overexpressing CL1-5 and ANGPTL1 knockdown H928 cells. Representative images of time-lapse cell tracker migration assay (top). Quantification of time-lapse cell tracker migration assay (bottom). (F–H) Measurement of the relative metastasis capability (tail vein injection) in ANGPTL1-overexpressing CL1-5 and ANGPTL1 knockdown H928 cells. (F) Representative images of lungs of mice. (G) Histological analyses of lung metastatic tumors by hematoxylin and eosin staining. T indicates tumor sites. Scale bars: 500 μm. (H) ANGPTL1 overexpression and knockdown and total numbers of lung metastatic nodules. Data are shown as mean ± SEM. *P < 0.05, **P < 0.01 (2-tailed Student’s t test).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Posted by 1 X users
Mentioned by 1 peer review sites
On 1 Facebook pages
62 readers on Mendeley
See more details