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

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

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54 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1082-1095
Number of pages14
JournalJournal of Clinical Investigation
Volume123
Issue number3
DOIs
Publication statusPublished - Mar 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Kuo, T. C., Tan, C. T., Chang, Y. W., Hong, C. C., Lee, W. J., Chen, M. W., Jeng, Y. M., Chiou, J., Yu, P., Chen, P. S., Wang, M. Y., Hsiao, M., Su, J. L., & Kuo, M. L. (2013). Angiopoietin-like protein 1 suppresses SLUG to inhibit cancer cell motility. Journal of Clinical Investigation, 123(3), 1082-1095. https://doi.org/10.1172/JCI64044