Galectin-1 promotes lung cancer tumor metastasis by potentiating integrin α6β4 and Notch1/Jagged2 signaling pathway

• Published in: Carcinogenesis (New York) 2013-06, Vol.34 (6), p.1370-1381
• Main Authors: Hsu, Ya-Ling, Wu, Cheng-Ying, Hung, Jen-Yu, Lin, Yi-Shiuan, Huang, Ming-Shyan, Kuo, Po-Lin
• Format: Article
• Language: English
• Subjects: Animals; Carcinoma, Lewis Lung - metabolism; Cell Line, Tumor; Cell Movement - genetics; Epithelial-Mesenchymal Transition; Galectin 1 - genetics; Galectin 1 - metabolism; Humans; Integrin alpha6beta4 - genetics; Integrin alpha6beta4 - metabolism; Integrin beta4 - genetics; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Jagged-2 Protein; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness - genetics; Neoplasm Metastasis; Neoplasm Transplantation; Phosphorylation - genetics; Proto-Oncogene Proteins c-akt - metabolism; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; RNA Interference; RNA, Small Interfering; Signal Transduction - genetics
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgt040

Lung cancer is a major cancer, leading in both incidence and mortality in the world, and metastasis underlies the majority of lung cancer-related deaths. Galectin-1, a glycan-binding protein, has been shown to be overexpressed in lung cancer and involved in tumor-mediated immune suppression. However, the functional role of galectin-1 in lung cancer per se remains unknown. We demonstrate that ectopic expression of galectin-1 in a low-metastatic CL1-0 lung cancer cell line promotes its migration, invasion and epithelial-mesenchymal transition. Conversely, we also show that suppression of galectin-1 expression in highly invasive CL1-5 and A549 cells inhibits migration and invasion of lung cancer cell and causes a mesenchymal-epithelial transition. These effects may be transduced by increasing the expression of integrin α6β4 and Notch1/Jagged2, which in turn co-operates in the phosphorylation of AKT. The effects of galectin-1 on cancer progression are reduced when integrin β4 and Notch1 are absent. Further study has indicated that galectin-1 knockdown prevents the spread of highly metastatic Lewis lung carcinoma in vivo. Our study suggests that galectin-1 represents a crucial regulator of lung cancer metastasis. Thus, the detection and targeted treatment of galectin-1-expressing cancer serves as a new therapeutic target for lung cancer.