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.
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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 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

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Figure 1

ANGPTL1 inversely correlates with stage, tumor status, lymph node status, invasion, and poor prognosis of lung cancer.

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ANGPTL1 inversely correlates with stage, tumor status, lymph node status...
(A) Staining with normal mouse IgG as negative control. Scale bar: 100 μm. (B) Strong staining of ANGPTL1 in normal lung bronchi. Scale bar: 100 μm. (C) Strong staining of ANGPTL1 (high expression). Scale bar: 100 μm. (D) Weak staining of ANGPTL1 (low expression). Scale bar: 100 μm. (E–H) Percentage of patients with high expression (++, +++) of ANGPTL1 and low expression (–, +) of ANGPTL1 according to different clinical parameters as follows: (E) tumor stage, (F) tumor status, (G) lymph node status, (H) cancer type. Numbers in bars represent the percentage of patients for each condition. AC, invasive adenocarcinoma; BAC, bronchoalveolar carcinoma. *P < 0.05, **P < 0.01 (n = 102 [E–G]; n = 70 [H]; 2-sided Pearson χ2 test). (I and J) Kaplan-Meier plot of (I) overall and (J) disease-free survival of patients with lung cancer, stratified by ANGPTL1 expression. The log-rank test was used to compare differences between groups (n = 102).